AMIR H. REZVANI 1,2 *, DAVID H. OVERSTREET 2, GEORGE A. MASON 2, DAVID S. JANOWSKY 2, MANI HAMEDI 2, E. CLARK, Jr 2 and YING YANG 2
|
|
- George Warren
- 5 years ago
- Views:
Transcription
1 Alcohol & Alcoholism Vol. 35, No. 1, pp , 2000 COMBINATION PHARMACOTHERAPY: A MIXTURE OF SMALL DOSES OF NALTREXONE, FLUOXETINE, AND A THYROTROPIN-RELEASING HORMONE ANALOGUE REDUCES ALCOHOL INTAKE IN THREE STRAINS OF ALCOHOL-PREFERRING RATS AMIR H. REZVANI 1,2 *, DAVID H. OVERSTREET 2, GEORGE A. MASON 2, DAVID S. JANOWSKY 2, MANI HAMEDI 2, E. CLARK, Jr 2 and YING YANG 2 1 Duke University Medical Center, Department of Psychiatry, Box 3412, Durham, NC and 2 The University of North Carolina School of Medicine, Chapel Hill, NC , USA (Received 6 April 1999; in revised form 15 June 1999; accepted 2 July 1999) Abstract It is common to treat some diseases with more than one medication simultaneously. Since more than one neurotransmitter system is involved in alcohol-seeking behaviour, then a therapeutic approach that targets more than one system should be more effective in reducing alcohol intake than one addressing a single system. To test this hypothesis, we compared the efficacy of low doses of individual drugs reported to reduce voluntary alcohol drinking to the efficacy of a mixture of these agents at the same low doses in reducing alcohol intake in three strains of alcohol-preferring rats (P, HAD, and Fawn-Hooded). After establishment of a stable baseline for alcohol intake in a continuous access paradigm, each rat received separate single i.p. injections of relatively low doses of either naltrexone (2.0 mg/kg), fluoxetine (1.0 mg/kg), the thyrotropin-releasing hormone analogue TA-0910 (0.2 mg/kg), a mixture of all three drugs, or the vehicle at 09:30. Each rat received all treatments, with an inter-injection washout period of at least 3 days. Alcohol and water intakes were measured at 6 and 24 h, and food intake was measured at 24 h, after the injection. Our results show that individual drugs did not significantly affect food, water, or alcohol intake. However, the mixture significantly reduced alcohol intake in all three strains, but had no effect on food intake. Similar results were obtained when the HAD rats received an oral dose of the individual drugs or the mixture. When P rats were given an i.p. injection of the mixture for 10 consecutive days, there was a continued suppressing effect. These findings show that a combination treatment designed to target simultaneously serotonergic, dopaminergic, and opioidergic systems can reduce alcohol intake, even though the doses of the individual drugs in the mixture are relatively low and ineffective when given singly. INTRODUCTION Alcoholism is a major health problem. In spite of large and intense efforts devoted to the treatment of this devastating disease, remediation of alcohol dependence remains a great challenge. In addition to disulfiram (antabuse) which is not an effective therapy for most alcoholics, several pharmacological agents including the opioid receptor antagonists naloxone and naltrexone (Froehlich et al., 1990; O Malley et al., 1992; Volpicelli et al., 1992), calcium channel blockers (Rezvani and Janowsky, 1990; Rezvani et al., 1991a; Pucilowski et al., 1992), dopaminergic agents (McBride et al., 1990; Hodge et al., 1993a), serotonin antagonists (Hodge et al., 1993b), serotonin uptake inhibitors (Rezvani et al., 1986, 1990, 1991b; McBride et al., 1990), and GABA-altering drugs (McBride et al., 1990) have been shown to reduce alcohol intake significantly or to diminish relapse in rodent models of alcoholism and in alcoholics. However, many of these compounds, in addition to reducing alcohol intake, may suppress appetite or have other undesirable effects. Thus, the development of suitable medications with greater selectivity toward excessive alcohol intake remains a major goal of alcohol researchers. It is common to treat some medical diseases with more than one medication simultaneously. This strategy is currently employed in the treatment of several major diseases and medical conditions including hypertension (Chalmers, 1993; Menard, 1993; Bakris and Williams, 1995; Levine et al., 1995; Prisant et al., 1995), depression (Tiller et al., 1992; Birkenhager et al., *Author to whom correspondence should be addressed. 1995), autoimmune diseases (Schumm-Draeger, 1993), cancer (Nakagawa et al., 1996), diabetes (Rosenthal, 1992), and nicotine addiction (Rose and Levin, 1992). There is considerable evidence that alcoholism is a multi-factorial disease that may involve impairment of central serotonergic (McBride et al., 1990; Rezvani et al., 1990; Rezvani and Grady, 1994; Grant, 1995), dopaminergic (McBride et al., 1990; Koob et al., 1994), opioidergic (Froehlich et al., 1990; Reid et al., 1991), and GABAergic systems (McBride et al., 1990). If deficits in more than one of these systems additively or synergistically contribute to alcohol-seeking behaviour, theoretically, a therapeutic approach that targets more than one system should be more effective than one addressing a single system. To test this hypothesis, we examined the effect on alcohol intake of administering simultaneously low doses of three pharmacological agents, which, at higher doses, have been shown to reduce alcohol intake in several strains of alcoholpreferring rats. For this initial study, we compared the effects of naltrexone, an opioid receptor antagonist; fluoxetine, a serotonin reuptake inhibitor; and TA-0910, a thyrotropinreleasing hormone (TRH) analogue with dopaminergic properties (Mason et al., 1994, 1996) to those of a mixture of these drugs on the intakes of alcohol, water, and food in three different strains of alcohol-preferring rats. The strains of rats used were: alcohol preferring (P, generation 40) rat and the high alcohol-drinking (HAD, generation 25) rat, which were developed at Indiana University by T. K. Li and colleagues (Li and McBride, 1995), and the inbred alcohol-preferring Fawn- Hooded (FH) strain which was developed by A. H. Rezvani at the University of North Carolina at Chapel Hill (Rezvani et al., 1990). These rats have been used extensively for studying Medical Council on Alcoholism
2 COMBINATION PHARMACOTHERAPY FOR ALCOHOLISM 77 compounds which reduce alcohol intake (Murphy et al., 1988; McBride et al., 1990; Rezvani et al., 1990, 1991a, 1992; Rezvani and Grady, 1994; Mason et al., 1997). We hypothesized that the combination treatment would be more potent than the individual compounds in suppressing alcohol intake, because more than one neurotransmitter system in the brain is involved in alcohol-seeking behaviour. Our findings do indeed support the hypothesis. MATERIALS AND METHODS Animals The three strains of alcohol-preferring rats were housed individually in stainless-steel wire mesh cages ( cm) under constant temperature of 21 ± 1 C and reversed 12 h light 12 h dark cycle (10:00 22:00 dark). These rats consume significantly more alcohol than their respective control strains: the selectively-bred alcohol non-preferring (NP), the low alcohol-drinking (LAD) rat, and the Wistar rat. The FH and P rats were derived from the Wistar rat. Water and food (Agway Prolab Rat/Mouse/Hamster 3000 formula, Agway, Syracuse, USA) were provided ad lib. Establishment of baseline Following the standard method (Murphy et al., 1988; Rezvani and Grady, 1994; Rezvani et al., 1995), rats were given 1 day access to water in a Richter tube followed by 3 days of free access to a solution of 10% (v/v) ethanol given as the only source of fluid. Thereafter, the rats were given a choice between alcohol and water for the remainder of the study. All experiments involved 24-h free access to food, water, and alcohol in a two-bottle choice paradigm. Preparation of drugs Naltrexone HCl (RBI, Natick, MA, USA), fluoxetine HCl (Eli Lilly and Co., Indianapolis, IN, USA), and TA-0910 (Tanabi, Seiyaku, Co. Ltd., Osaka, Japan) were dissolved in saline freshly each day. The concentrations of naltrexone, fluoxetine, and TA-0910 in the mixture or in separate treatments were 2.0, 1.0, and 0.2 mg/ml, respectively. The doses chosen for these experiments are relatively small and although they may reduce alcohol intake in a 1 2 h scheduled access paradigm (Froehlich et al., 1990; McBride et al., 1990; Froehlich and Li, 1993), they exert no significant effect on alcohol intake in alcohol-preferring rats in the 24-h access protocol. The volume of systemic injections was always 1 ml/kg and that for oral administration was 4 ml/kg. Based on our experience comparing the potencies of compounds given systemically and orally, an oral dose three times that given i.p. will exert a similar effect (Overstreet et al., 1996). Alcohol solutions (10%, v/v) were prepared every 2 days from distilled water and a stock solution of 95% reagent grade ethanol. Experimental protocols Experiment 1: acute systemic administration. After establishment of a stable baseline for alcohol and water intakes, animals were maintained on a continuous access to alcohol and water via a two-bottle choice paradigm for about 2 months. Then, rats (n = 8 for P and HAD rats and n = 15 for FH rats) received a single i.p. injection of the saline vehicle, naltrexone (2.0 mg/kg), fluoxetine (1.0 mg/kg), TA-0910 (0.2 mg/kg), or a mixture of the three drugs at 09:30. Alcohol and water intakes were measured at 6 and 24 h after the injection. Food intake was measured 24 h after the injection. Each rat received all five treatments, separated by washout periods of at least 3 days. Experiment 2: acute oral administration. Any compound, which might be used in human subjects, should be orally active. To investigate the effect of the oral administration of the mixture on alcohol intake, the same HAD rats used in experiment 1 received a single oral administration of either the saline vehicle, naltrexone (6.0 mg/kg), fluoxetine (3.0 mg/kg), TA-0910 (0.6 mg/kg), or the mixture of the three drugs at 09:30. All solutions were delivered by gastric intubation into the stomach through a special ball-tipped 16-gauge stainlesssteel gavage needle (Beckton Dickinson) (Rezvani et al., 1986). Alcohol and water intakes were measured at 6 and 24 h after drug administration, whereas food intake was measured 24 h after the treatment. Each rat received all five treatments separated by washout periods of at least 3 days. Experiment 3: chronic systemic administration. It has been shown that tolerance develops to the suppressing effects of naltrexone, fluoxetine, and TA-0910 and some other drugs on alcohol intake in rats (Rezvani et al., 1993; Mason et al., 1994; Cowen et al., 1999). To test this phenomenon with the mixture, a chronic experiment was conducted with nine adult male P rats. After establishment of stable baselines for alcohol and water intakes, and following a cross-over design, the mixture or vehicle was given i.p. once a day for 10 consecutive days. Alcohol and water intakes were measured at 6 and 24 h after the treatment, whereas food intake was measured 24 h after the treatment. Each rat received both treatments, and a washout period of 3 days was imposed between treatments. Statistical analysis The results were expressed as means ± standard error of means (SEM). Alcohol intake (g/kg) was calculated by multiplying the volume of alcohol consumed by 10% and (ethanol density)/animal body weight in kg. Alcohol preference, expressed as a percentage, was calculated as follows: (volume of alcohol consumed in ml/total fluid intake in ml) 100 (Rezvani et al., 1990; Rezvani and Grady, 1994). Statistical differences between different groups were determined using analysis of variance followed by Newman Keuls protected t-test. RESULTS Experiment 1: acute systemic administration Baseline consumption levels of alcohol were 8.47 ± 0.73, 6.9 ± 0.8, and 6.1 ± 0.56 g/kg/day for P, HAD, and FH rats, respectively (means ± SEM). Compared to the vehicle, a single injection of the mixture significantly suppressed alcohol intake (Fig. 1A) and alcohol preference (Fig. 1B) in P rats. Separately administered naltrexone or TA-0910 did not induce a significant effect on 6-h alcohol intake and alcohol preference, and the effect of fluoxetine was significantly less than that of the mixture of drugs (Fig. 1A). The mixture of drugs, but not the individual drugs, significantly increased water intake at 6 h (Fig. 1C). Neither the mixture of drugs nor the individual drugs changed food intake (Fig. 1D).
3 78 A. H. REZVANI et al. Fig. 1. Effects of a single i.p. administration of naltrexone, fluoxetine, TA-0910, or a mixture of the three drugs on 6-h alcohol intake and alcohol preference and water and food intake in alcohol-preferring P rats. Rats had free 24-h access to water, food, and a solution of 10% (v/v) alcohol. Drug doses were as follows: naltrexone (2 mg/kg), fluoxetine (1 mg/kg), TA-0910 (0.2 mg/kg). *P < 0.05 and **P < vs saline. In both HAD and FH rats, systemic administration of the mixture, but not its individual constituents, also significantly reduced alcohol intake (Fig. 2). However, contrary to P rats, water intake was not significantly affected in these two strains (Table 1). Food intake was also unaffected by the mixture or by individual drugs in FH or HAD rats (Table 1). Experiment 2: acute oral administration Compared with the vehicle, oral administration of the mixture, and fluoxetine alone, significantly reduced alcohol intake in HAD rats at 6 h (Fig. 3). However, fluoxetine administration was significantly (P < 0.01) less effective than the mixture (Fig. 3) and also significantly (P < 0.01) reduced water intake in HAD rats (Table 2). Neither the mixture nor its constituents reduced the 24-h food intake (Table 2). Oral administration of naltrexone or TA-0910 alone did not exert any significant effects on alcohol, food or water intakes (Fig. 3 and Table 2). Experiment 3: chronic systemic administration Repeated single daily i.p. administration of the mixture for 10 consecutive days, but not the vehicle, significantly reduced alcohol intake in P rats, both at 6 (P < , Fig. 4A) and 24 h (P < 0.004, Fig. 4B) without development of tolerance to the suppressant effect of the mixture on alcohol intake. Chronic administration of the mixture to P rats also significantly (P < 0.03) increased the water intake at 6 h (Fig. 5A) but not at 24 h. (Fig. 5B), whereas food intake was increased significantly (P < ) following chronic administration of the mixture to these rats (Fig. 6). DISCUSSION The present study shows that a mixture composed of relatively low doses of three different kinds of alcohol intakesuppressing drugs can significantly reduce alcohol intake
4 COMBINATION PHARMACOTHERAPY FOR ALCOHOLISM 79 Fig. 3. Effects of a single oral administration of naltrexone, fluoxetine, TA-0910, or a mixture of the three drugs on 6-h alcohol intake in HAD rats. Rats had free 24-h access to water, food, and a solution of 10% alcohol. The doses of the drugs were as follows: naltrexone (6 mg/kg), fluoxetine (3 mg/kg), TA-0910 (0.6 mg/kg). *P < 0.05 and **P < 0.01 vs saline. Fig. 2. Effects of a single i.p. administration of naltrexone, fluoxetine, TA-0910, or a mixture of the three drugs on 6-h alcohol intake in FH and HAD rats. Rats had free 24-h access to water, food, and a solution of 10% (v/v) alcohol. Doses of drugs were as in Fig. 1. *P < 0.02 and **P < 0.01 vs saline. Table 1. Effects of a single systemic (i.p.) administration of the mixture and individual constituents on water and food intake in FH and HAD rats Intakes Saline Naltx Fluox TA-0910 Mixture FH rats Water 14 ± ± ± ± ± 2.0 (g/kg/6 h) Food 47 ± ± ± ± ± 2.0 (g/kg/day) HAD rats Water 6.0 ± ± ± ± ± 3.0 (g/kg/6 h) Food 52 ± ± 6 48 ± ± ± 5.0 (g/kg/day) Naltx = naltrexone, 2 mg/kg; Fluox = fluoxetine, 1 mg/kg; TA-0910, 0.2 mg/kg. Values are means ± SEM (n = for FH and eight for HAD rats). Table 2. Effects of oral administration of the mixture and individual constituents on water and food intakes in eight HAD rats Intakes Saline Naltx Fluox TA-0910 Mixture Water 3.0 ± ± ± 0.3* 2.0 ± ± 1.0 (g/kg/6 h) Food 47 ± ± ± ± ± 6.0 (g/kg/day) Naltx = naltrexone, 6 mg/kg; Fluox = fluoxetine, 3 mg/kg; TA-0910, 0.6 mg/kg. Values are means ± SEM. *Significantly different from saline at P < without altering food consumption in three different strains of alcohol-preferring rats. Two of the component drugs, fluoxetine and naltrexone, have been shown to reduce food intake and body weight in rats when administered separately at doses that individually suppress alcohol intake (Murphy et al., 1988; Overstreet et al., 1995; Rezvani et al., 1996; Gardell et al., 1997). The fact that the mixture of drugs was more efficacious in suppressing alcohol intake than any of the constituents alone, but did not suppress food intake, suggests that the serotonergic, dopaminergic, and opioidergic systems may interact synergistically or additively to reduce alcohol consumption but not food intake. Thus, the combination treatment may produce fewer or weaker non-specific side-effects, such as appetite suppression, which might be counter-productive in treating alcoholism. The suppressant effects of fluoxetine and naltrexone are not specific to alcohol. Murphy et al. (1988) and Gardell et al. (1997) have shown that fluoxetine, in doses which reduce alcohol intake, prevents growth, and this drug is used to suppress appetite in humans. Naltrexone also has been shown to reduce body weight in rats (Gardell et al., 1997). These effects could be undesirable in chronic alcoholics, who are frequently malnourished. In the present studies, neither food
5 80 A. H. REZVANI et al. Fig. 4. Effects of repeated i.p. administration of saline or the mixture of drugs (naltrexone + fluoxetine + TA-0910) on alcohol intake at 6 and 24 h in P rats. Rats had free 24-h access to water, food, and a solution of 10% alcohol. The i.p. doses were the same as those given in the single experiments of Fig. 1. F(17,1) = 62.8, P < for 6-h data and F(17,1) = 11.5, P < for 24-h data. *P < 0.05 and **P < 0.01 vs the corresponding saline values. nor water intake was reduced at 24 h by a single injection of the mixture or of its constituent drugs; however, when fluoxetine was given orally to HAD rats, it significantly reduced both alcohol and water intakes, indicating a non-specific effect. We reported previously that the administration of a single large dose (0.75 mg/kg) of TA-0910 into P rats increased food but not total calorie intake (Rezvani et al., 1992). It is possible that the presence of TA-0910 in the mixture may have counteracted any suppressing effect that fluoxetine and naltrexone together may have had on food intake, resulting in a net outcome of no change in food intake. Our results suggest that this combination treatment is relatively more potent than its individual constituent drugs in reducing alcohol intake, and more selective than larger doses of fluoxetine or naltrexone, which reduce alcohol intake. However, since food intake was not measured at 6 h, it is not clear whether food intake was decreased during this period but was compensated for in the remainder of the 24-h test period. Although the mechanisms underlying the suppressant effect of the mixture of drugs on alcohol intake were not addressed by the present study, a review of current literature suggests that the mixture might exert its effect by interacting with central dopamine (DA), serotonin (5-HT), and opioids, each Fig. 5. Effects of repeated i.p. administration of saline or the mixture of drugs (naltrexone + fluoxetine + TA-0910) on water intake in P rats. Rats had free 24-h access to water, food, and a solution of 10% alcohol. Drug administration details are as in Fig. 4. F(17,1) = 5.5, P < 0.03 for 6-h data and F(17,1) = 2.4, P = 0.14 for 24-h data. *P < 0.05 and **P < 0.01 vs the corresponding saline values. Fig. 6. Effects of repeated i.p. administration of saline or the mixture of drugs (naltrexone + fluoxetine + TA-0910) on food intake in P rats. Rats had free 24-h access to water, food, and a solution of 10% alcohol. Other details are as in Fig. 5. F(17,1) = 25.9, P < *P < 0.05 and **P < 0.01 vs the corresponding saline values.
6 COMBINATION PHARMACOTHERAPY FOR ALCOHOLISM 81 of which may be involved in alcohol-seeking behaviour in animals and humans (see Introduction). The mesolimbic DA system has been implicated in the reinforcing properties of abused substances, including alcohol (DiChiara and Imperato, 1988; Koob et al., 1994). Based on these findings, it is speculated that the mixture may exert its suppressant effect on alcohol intake by modulating, at least in part, the dopaminergic system. There is evidence that each component of the mixture stimulates the reward system by enhancing DA release in the mesolimbic pathway. Behavioural studies indicate that TA-0910 stimulates DA release in the nucleus accumbens (Yamamura et al., 1991). The development of a partial crosstolerance between TA-0910 and the DA agonist bromocriptine with respect to the attenuating effect on alcohol intake in P rats (Mason et al., 1994) and the antagonism of the suppressant effect of TA-0910 on alcohol intake by the DA D2 antagonist eticlopride (Mason et al., 1997) further support a dopaminergic mechanism in the suppressant effect of TA-0910 on alcohol intake. Fluoxetine has been demonstrated to release DA in the prefrontal cortex of freely moving rats by stimulating local 5-HT 3 receptors (Tanada et al., 1995). There is also evidence of interaction between the opioidergic and dopaminergic systems, including anatomic co-localization of endogenous opioids and DA in the brain which reflects the interplay between these two systems. It has also been shown that microinjection of the selective µ-opioid receptor antagonists D-Pen-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH 2 and β-funaltrexamine into the ventral tegmental area produces increases in extracellular DA and DA metabolite concentrations in the ventral striatum (Devine et al., 1993). However, there are also conflicting reports that peripheral administration of opioid antagonists blocks DA release (Benjamin et al., 1993). Thus, it is unclear whether administration of naltrexone in the mixture increases mesolimbic DA transmission. Nevertheless, in preliminary experiments, we found that the mixture of the three drugs was more effective in reducing the 6-h alcohol intake than a combination of equivalent doses of TA-0910 and fluoxetine, suggesting that, at the dose we used, naltrexone does not counteract the effects of fluoxetine and TA-0910 and may enhance their suppressive effects on alcohol intake by an as yet unknown mechanism(s). Therefore, the suppressant action of the mixture on alcohol intake may indeed result from enhancement of DA release in the mesolimbic system that, by substituting for alcoholmediated enhancement of DA release, reduces the motivation to drink. It is also possible that drug drug interactions play a role in the effect of the mixture in reducing alcohol intake. For example, one compound in the mixture may influence the pharmacokinetics of another compound, thus affecting its action on alcohol intake. However, this appears unlikely, because we used small doses of each drug in the mixture and the effect of the mixture on alcohol intake was apparent as early as 2 h following intake. Comparing the blood levels of the drugs and their active metabolites when given alone with those obtained when the mixture is given is needed to resolve this issue. Recently, several groups have examined the effects of different combinations of drugs on alcohol intake with mixed results. Gardell et al. (1997) have shown that the suppressing effect of a combination of naltrexone (5 mg/kg) and fluoxetine (5 mg/kg) on alcohol intake is no different from those of either drug in Sprague Dawley rats. However, in a preliminary study, Zink et al. (1997) reported that naltrexone and fluoxetine act synergistically to decrease alcohol intake in P rats. Similar findings have been reported with a combination of naltrexone and ondansetron, a 5-HT 3 receptor antagonist, in mice and rats (Le and Sellers, 1994). Since the effects of these combinations on food and water intakes have not been reported, we are unable to compare all of the effects of these combinations with our results. Concurrent administration of amperozide, a 5-HT 2a receptor antagonist, and naltrexone has also been shown to suppress volitional drinking of alcohol in HAD rats, without side-effects on food and water intakes. The suppressing effect of this combination on alcohol intake was greater than that of the individual drugs (Lankford and Myers, 1996). In a pilot clinical study, Williams and Mason (1997) have shown that a combination of nalmefene and sertraline is more effective than sertraline and placebo in alcohol-dependent patients who failed to respond to nalmefene alone, suggesting the benefit of combination pharmacotherapy for the treatment of alcohol dependence. In another small clinical study, Salloum et al. (1998) combined naltrexone with a selective serotonin reuptake inhibitor (SSRI) for the treatment of patients diagnosed as currently alcohol-dependent and depressed. The naltrexone SSRI combination reduced drinking from 49 drinks per week to six drinks per week. In addition, depressive symptoms improved. Farren et al. (1997) have also examined the effects of the combination of a SSRI (sertraline, 50 and 100 mg/day) and naltrexone (50 mg/day) in the treatment of alcoholism. Using the Obsessive Compulsive Drinking Scale (Anton et al., 1996) the patients on combination therapy tended to report lower levels of craving for alcohol at the end of 10 weeks of treatment, than in the naltrexone only group. It should be mentioned that, although these findings are promising, they should be considered preliminary as the sample size was small in all of these clinical studies. In summary, the present results demonstrate that combination pharmacotherapy can be more potent and in some cases more specific in reducing alcohol intake than monopharmacotherapy in alcohol-preferring rats. These results show that a mixture of low doses of naltrexone, fluoxetine, and TA-0910, is more potent than any of the individual drugs in suppressing alcohol intake, without producing a significant effect on 24-h food intake. These promising preclinical findings suggest that the strategy of combination pharmacotherapy should be tested in alcoholics. Acknowledgements We greatly appreciate the generous gifts of fluoxetine from Eli Lilly and Co. and TA-0910 from Tanabi Inc., Japan. We also thank Dr T.-K. Li and his colleagues at Indiana University (P50-AA07611) for providing the P and HAD rats. This work was supported in part by a grant from the NIAAA (AA07809). REFERENCES Anton, R. F., Moak, D. H. and Latham, P. K. (1996) The Obsessive Compulsive Drinking Scale: a new method of assessing outcome in alcoholism treatment studies. Archives of General Psychiatry 53, Bakris, G. L. and Williams, B. (1995) Angiotensin converting enzyme inhibitors and calcium antagonists alone or combined: does the
7 82 A. H. REZVANI et al. progression of diabetic renal disease differ? Journal of Hypertension 13, S95 S101. Benjamin, D., Grant, E. R. and Pohorecky, L. A. (1993) Naltrexone reverses ethanol-induced dopamine release in the nucleus accumbens in awake, freely moving rats. Brain Research 621, Birkenhager, T. K., Moleman, P. and Nolen, W. A. (1995) Benzodiazepines for depression? A review of the literature. International Clinical Psychopharmacology 10, Chalmers, J. (1993) The place of combination therapy in the treatment of hypertension. Clinical and Experimental Hypertension 15, Cowen, M. S., Rezvani, A. H., Jarrott, B. and Lawerence, A. J. (1999) Ethanol consumption by Fawn-Hooded rats following abstinence: effects of naltrexone and changes in µ-opioid receptor density. Alcoholism: Clinical and Experimental Research 23, Devine, D. P., Leone, P. and Wise, R. A. (1993) Mesolimbic dopamine neurotransmission by administration of µ-opioid receptor antagonists. European Journal of Pharmacology 24, DiChiara, G. and Imperato, A. (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proceeding of the National Academy of Sciences of the USA 85, Farren, C. K., Catapano, D. and O Malley, S. (1997) Sertraline with naltrexone versus naltrexone alone in the treatment of alcohol dependence. Alcoholism: Clinical and Experimental Research 21 (suppl.), 64 (Abstract no. 366). Froehlich, J. C. and Li, T.-K. (1993) Recent developments in alcoholism: opioid peptides. Recent Developments in Alcoholism 11, Froehlich, J. C., Harts, J., Lumeng, L. and Li, T.-K. (1990) Naloxone attenuates voluntary ethanol intake in rats selectively bred for high ethanol preference. Pharmacology, Biochemistry and Behavior 35, Gardell, L. R., Whalen, C. A., Chattophadyay, S., Cavallaro, C. A., Hubbell, C. L. and Reid, L. D. (1997) Combination of naltrexone and fluoxetine on rats propensity to take alcoholic beverage. Alcoholism: Clinical and Experimental Research 21, Grant, K. A. (1995) The role of 5-HT 3 receptors in drug dependence. Drug and Alcohol Dependence 38, Hodge, C. A., Haraguchi, M., Erickson, H. L. and Samson, H. H. (1993a) Ventral tegmental microinjections of quinpirole decrease ethanol and sucrose-reinforced responding. Alcoholism: Clinical and Experimental Research 17, Hodge, C. A., Samson, H. H., Lewis, R. S. and Erickson, H. L. (1993b) Specific decreases in ethanol but not water-reinforced responding produced by the 5-HT 3 antagonist ICS Alcohol 10, Koob, G. F., Rassnick, S., Heinrichs, S. and Weiss, F. (1994) Alcohol, the reward system and dependence. EXS 71, Lankford, M. F. and Myers, R. D. (1996) Opiate and 5-HT 2a receptors in alcohol drinking: preference in HAD rats is inhibited by combination treatment with naltrexone and amperozide. Alcohol 13, Le, A. D. and Sellers, E. M. (1994) Interaction between opiate and 5-HT 3 receptor antagonists in the regulation of alcohol intake. Alcohol and Alcoholism 29 (suppl. 2), Levine, J. H., Ferdinand, K. C., Cargo, P., Laine, H. and Lefkowitz, M. (1995) Additive effects of verapamil and enalapril in the treatment of mild to moderate hypertension. American Journal of Hypertension 8, Li, T.-K. and McBride, W. J. (1995) Pharmacogenetic models of alcoholism. Clinical Neuroscience 3, Mason, G. A., Rezvani, A. H., Grady, D. R. and Garbutt, J. C. (1994) The subchronic effects of the TRH analog TA-0910 and bromocriptine on alcohol preference in alcohol-preferring rats: development of tolerance and cross-tolerance. Alcoholism: Clinical and Experimental Research 18, Mason, G. A., Rezvani, A. H., Overstreet, D. H. and Garbutt, J. C. (1996) The thyrotropin releasing hormone analog TA-0910 reduces voluntary alcohol intake of P rats subchronically in a limited scheduled access paradigm. Alcoholism: Clinical and Experimental Research 20, Mason, G. A., Rezvani, A. H., Overstreet, D. H., Hamedi, M., Walker, C. H., Yang, Y. and Garbutt, J. C. (1997) Involvement of dopamine D2 receptors in the suppressive effect of the thyrotropin releasing hormone analog TA-0910 on alcohol intake in P rats. Alcoholism: Clinical and Experimental Research 21, McBride, W. J., Murphy, J. M., Lumeng, L. and Li, T.-K. (1990) Serotonin, dopamine and GABA involvement in alcohol drinking of selectively bred rats. Alcohol 7, Menard, J. (1993) Critical assessment of combination therapy development. Blood Pressure 1, 5 9. Murphy, J. M., Waller, M. B., Gatto, G. J., McBride, W. J., Lumeng, L. and Li, T.-K. (1988) Effects of fluoxetine on the intragastric selfadministration of ethanol in the alcohol preferring P line of rats. Alcohol 5, Nakagawa, H., Kobayashi, K., Tono, T., Fukuda, K., Shinn, E., Mishima, H., YagyKobayashi, T. and Kikkawa N. (1996) Combination of intra-hepatic arterial infusion of low dose cisplatin and oral administration of high-dose doxyfluridine for patients with live metastases of gastric cancer. Japanese Journal of Cancer and Chemotherapy 23, O Malley, S. S., Jaffe, A. J., Chang, G., Schottenfeld, R. S., Meyer, R. E. and Rounsaville, B. (1992) Naltrexone and coping skills therapy for alcohol dependence. Archives of General Psychiatry 49, Overstreet, D. H., Rezvani, A. H. and Kampov-Polevoy, A. B. (1995) Strain-dependent suppressant effects of dopaminergic, serotonergic and opioidergic agents on alcohol intake. Society for Neuroscience Abstract Overstreet, D. H., Lee, Y. W., Rezvani, A. H., Pei, Y. H., Criswell, H. E. and Janowsky, D. S. (1996) Suppression of alcohol intake after administration of the Chinese herbal medicine, NPI-028, and its derivatives. Alcoholism: Clinical and Experimental Research 20, Prisant, L. M., Weir, M. R., Papademetriou, V., Weber, M. A., Adegbile, I. A., Alemayehu, D., Lefkowitz, M. P. and Carr, A. A. (1995) Lowdose drug combination therapy: an alternative first-line approach to hypertension treatment. American Heart Journal 130, Pucilowski, O., Rezvani, A. H. and Janowsky, D. S. (1992) Suppression of alcohol and saccharin preference in rats by a novel Ca 2+ channel inhibitor, GOE Psychopharmacology 107, Reid, L. D., Delconte, J. D., Nichols, M. L., Bilsky, E. J. and Hubbell, C. L. (1991) Tests of opioid deficiency hypotheses of alcoholism. Alcohol 8, Rezvani, A. H. and Janowsky, D. S. (1990) Decrease of alcohol consumption by verapamil in alcohol preferring rats. Progress in Neuro- Psychopharmacology and Biological Psychiatry 14, Rezvani, A. H. and Grady, D. R. (1994) Suppression of alcohol consumption by fenfluramine in Fawn-Hooded rats with serotonin dysfunction. Pharmacology, Biochemistry and Behavior 48, Rezvani, A. H., Crovi, S. I., Mack, C. M. and Myers, R. D. (1986) Central Ca 2+ -channel blockade reverses ethanol induced poikilothermia in the rat. Alcohol 3, Rezvani, A. H., Overstreet, D. H. and Janowsky D. S. (1990) Genetic serotonin deficiency and alcohol preference in the Fawn-Hooded rats. Alcohol and Alcoholism 25, Rezvani, A. H., Grady, D. R. and Janowsky, D. S. (1991a) Effect of Ca 2+ -channel blockers on alcohol preference in alcohol-drinking monkeys. Alcohol and Alcoholism 26, Rezvani, A. H., Overstreet, D. H. and Janowsky, D. S. (1991b) Druginduced reductions in ethanol intake in alcohol preferring and Fawn- Hooded rats. Alcohol and Alcoholism 26 (suppl. 1), Rezvani, A. H., Garbutt, J. C., Shimoda, K., Garges, P. L., Janowsky, D. S. and Mason, G. A. (1992) Attenuation of alcohol preference in alcohol-preferring rats by a novel TRH analogue, TA Alcoholism: Clinical and Experimental Research 16, Rezvani, A. H., Mason, G. A., Garbutt, J. C., Janowsky, D. S. and Overstreet, D. H. (1993) Reductions of tolerance to anti-craving drugs for alcohol. Alcoholism: Clinical and Experimental Research 17, 515. Rezvani, A. H., Overstreet, D. H. and Lee, Y. W. (1995) Attenuation of alcohol intake by Ibogaine in three strains of alcohol preferring rats. Pharmacology, Biochemistry and Behavior 52, Rezvani, A. H., Overstreet, D. H. and McArthur, R. (1996) Amperozide, a 5-HT-2a receptor antagonist, is more effective in reducing alcohol intake than fluoxetine or duloxetine. Society for Neuroscience Abstract Rose, J. E. and Levin, E. D. (1992) Concurrent agonist antagonist administration for the analysis and treatment of drug dependence. Pharmacology, Biochemistry and Behavior 41,
8 COMBINATION PHARMACOTHERAPY FOR ALCOHOLISM 83 Rosenthal, T. C. (1992) Combining insulin and oral agents in diabetes: indications and controversies. American Family Physician 46, Salloum, I. M., Cornelius, J. R., Thase, M. E., Daley, D. C., Kirisci, L. and Spotts C. (1998) Naltrexone utility in depressed alcoholics. Psychopharmacology Bulletin 34, Schumm-Draeger, P. M. (1993) Drug therapy of goiter. Iodine, thyroid hormones or combined therapy. Zeitschrift fur die Gesamte Innere Medizin und Ihre Grenzgebiete 48, Tanada, G., Frau, R. and DiChiara, G. (1995) Local 5-HT3 receptors mediate fluoxetine but not desipramine-induced increase of extracellular dopamine in the prefrontal cortex. Psychopharmacology 119, Tiller, J. W., Mitchell, P. and Burrows, G. D. (1992) Monoamine oxidase inhibitors (MAOI) or reversible inhibitors of monoamine oxidase (RIMA)/tricyclic antidepressant (TCA) combination therapy. Australian and New Zealand Journal of Psychiatry 26, Volpicelli, J. R., Alterman, A. I., Hayashida, M. and O Brien, C. P. (1992) Naltrexone in the treatment of alcohol dependence. Archives of General Psychiatry 49, Williams, L. D. and Mason, B. J. (1997) Combination pharmacotherapy in nalmefene non-responders. Alcoholism: Clinical and Experimental Research, 21 (suppl.), 33, Abstract 179. Yamamura, M., Kinoshita, K., Nakagawa, H. and Ishida, R. (1991) Pharmacological study of TA-0910, a new thyrotropin-releasing hormone (TRH) analog (II): involvement of the DA system in locomotor stimulating action of TA Japanese Journal of Pharmacology 55, Zink, R. W., Rohrbach, K. and Froehlich, J. C. (1997) Naltrexone and fluoxetine act synergistically to decrease alcohol intake. Alcoholism: Clinical and Experimental Research 21 (suppl.), 105, Abstract no. 606.
ATTENUATION OF ALCOHOL INTAKE BY EXTRACT OF HYPERICUM PERFORATUM (ST JOHN S WORT) IN TWO DIFFERENT STRAINS OF ALCOHOL-PREFERRING RATS
Alcohol & Alcoholism Vol. 34, No. 5, pp. 699 705, 1999 ATTENUATION OF ALCOHOL INTAKE BY EXTRACT OF HYPERICUM PERFORATUM (ST JOHN S WORT) IN TWO DIFFERENT STRAINS OF ALCOHOL-PREFERRING RATS AMIR H. REZVANI*,
More informationLong term pharmacotherapy for Alcohol Dependence: Anti Craving agents
Long term pharmacotherapy for Alcohol Dependence: Anti Craving agents Myth or Reality? Complete Recovery means a medication-free state True or False? Treatment of Alcoholism Assessment Motivation Alcohol
More information6B / Boswell, Grant and Slutske Day 2 August 14, 2008
Pharmacological Treatment of Pathological Gambling Jon E. Grant, JD, MD, MPH Associate Professor University of Minnesota School of Medicine Minneapolis, MN Disclosure Information I have the following financial
More informationEffect of the combination of naltrexone and acamprosate on alcohol intake in mice
Blackwell Science, LtdOxford, UKPCNPsychiatry and Clinical Neurosciences1323-131624 Blackwell Science Pty LtdFebruary 24581336Original ArticleNaltrexone and acamprosates-g. Kim et al. Psychiatry and Clinical
More informationDEVELOPMENT OF ALCOHOL DEPRIVATION EFFECT IN RATS: LACK OF CORRELATION WITH SACCHARIN DRINKING AND LOCOMOTOR ACTIVITY
Alcohol & Alcoholism Vol. 34, No. 4, pp. 542 550, 1999 DEVELOPMENT OF ALCOHOL DEPRIVATION EFFECT IN RATS: LACK OF CORRELATION WITH SACCHARIN DRINKING AND LOCOMOTOR ACTIVITY ELIZA KOROS 1, JERZY PIASECKI
More informationMOLECULAR BIOLOGY OF DRUG ADDICTION. Sylvane Desrivières, SGDP Centre
1 MOLECULAR BIOLOGY OF DRUG ADDICTION Sylvane Desrivières, SGDP Centre Reward 2 Humans, as well as other organisms engage in behaviours that are rewarding The pleasurable feelings provide positive reinforcement
More informationprocesses in the central nervous system (CNS), affecting many of the during the course of ethanol treatment. Ethanol stimulates the release of
INTRODUCTION INTRODUCTION Neuroscience research is essential for understanding the biological basis of ethanol-related brain alterations and for identifying the molecular targets for therapeutic compounds
More informationNEUROBIOLOGY ALCOHOLISM
NEUROBIOLOGY ALCOHOLISM THERE HAS BEEN A MAJOR THEORETICAL SHIFT IN MEDICATION DEVELOPMENT IN ALCOHOLISM Driven by animal models of intermittent ethanol administration followed by termination, then access
More informationThe future of pharmacological treatment.
The future of pharmacological treatment. Anne Lingford-Hughes Professor of Addiction Biology, Imperial College. Hon Consultant CNWL NHS Foundation Trust. What substances and when? What Nicotine Alcohol
More informationAmerica is a drugged society
Overview of Drug Abuse Basic Considerations. M. Imad Damaj, Ph.D. Associate Professor Dept. of Pharmacology/Toxicology, Virginia Commonwealth University America is a drugged society 90% of all drugs manufactured
More informationPharmacotherapy for Alcohol Dependence
Evidence Report/Technology Assessment: Number 3 Pharmacotherapy for Alcohol Dependence Summary Under its Evidence-Based Practice Program, the Agency for Health Care Policy and Research (AHCPR) is developing
More informationDrugs, The Brain, and Behavior
Drugs, The Brain, and Behavior John Nyby Department of Biological Sciences Lehigh University What is a drug? Difficult to define Know it when you see it Neuroactive vs Non-Neuroactive drugs Two major types
More informationPATHOLOGICAL GAMBLING: NEUROBIOLOGY
CHAPTER 11 PATHOLOGICAL GAMBLING: NEUROBIOLOGY AND PHARMACOLOGICAL TREATMENT Dominic Lim & Doug Sellman Pathological gambling, a highly disabling condition at the severe end of the spectrum of gambling
More informationRiunione Monotematica AISF 2017 Roma 5 Ottobre Management of Alcohol Use Disorders in Patients with Alcoholic Liver Disease
Riunione Monotematica AISF 2017 Roma 5 Ottobre 2017 Management of Alcohol Use Disorders in Patients with Alcoholic Liver Disease Lorenzo Leggio, M.D., Ph.D., M.Sc. Lorenzo Leggio, M.D., Ph.D., M.Sc. Il
More informationGhrelin mediates stressinduced. behavior in mice. Chuang et al 2011 L3: Love, Lust, Labor
Ghrelin mediates stressinduced food-reward behavior in mice Chuang et al 2011 L3: Love, Lust, Labor Agenda Introduction What is Ghrelin? Previous Models New model Methods Results Discussion Conclusion
More informationOPIOID ANTAGONISTS IN THE TREATMENT OF ALCOHOL DEPENDENCE: CLINICAL EFFICACY AND PREVENTION OF RELAPSE
Alcohol & Alcoholism, Vol. 31, Suppl. 1, pp. 77-81, 1996 OPIOID ANTAGONISTS IN THE TREATMENT OF ALCOHOL DEPENDENCE: CLINICAL EFFICACY AND PREVENTION OF RELAPSE STEPHANIE S. O'MALLEY Department of Psychiatry.
More informationDownloaded from Interaction of neurotransmitters with alcohol in cases of depression
INTERACTION OF NEUROTRANSMITTERS WITH ALCOHOL IN CASES OF DEPRESSION Dr. Anil Batta Professor & Head, Dep t of Medical Biochemistry GGS medical college, Baba Farid Univ.of health sciences, Faridkot. ISSN
More informationContribution of the Opioid System to Alcohol Aversion and Alcohol Drinking Behavior 1
0022-3565/98/2871-0284$03.00/0 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 287, No. 1 Copyright 1998 by The American Society for Pharmacology and Experimental Therapeutics Printed in
More informationEVALUATION OF ANTIDEPRESSANT ACTIVITY OF ONDANSETRON IN ALBINO MICE
EVALUATION OF ANTIDEPRESSANT ACTIVITY OF ONDANSETRON IN ALBINO MICE *Janardhan M. 1, Anil kumar G. 1 and Naveen Kumar T. 2 1 Department of Pharmacology, Kamineni Institute of Medical Sciences and Research,
More informationKnowing How Gamblers Think: Improving Treatment Outcomes
Knowing How Gamblers Think: Improving Treatment Outcomes Jon E. Grant, JD, MD, MPH Professor University of Minnesota School of Medicine Minneapolis, MN Disclosure Information I have the following financial
More informationManagement of Tobacco Dependence. Dr. Lokesh Kumar Singh Associate Professor Department of Psychiatry AIIMS, Raipur
Management of Tobacco Dependence Dr. Lokesh Kumar Singh Associate Professor Department of Psychiatry AIIMS, Raipur Difficult to identify any other condition that presents such a mix of lethality, prevalence,
More informationBASIC VOLUME. Elements of Drug Dependence Treatment
BASIC VOLUME Elements of Drug Dependence Treatment Module 3 Principles of CBT and relapse prevention strategies Introduction to Cognitive Behavioural Therapy Basics of pharmacological treatment Workshop
More informationMk-801 Administration in Adolescent Male Rats and Cocaine Conditioned Place
Mk-801 Administration in Adolescent Male Rats and Cocaine Conditioned Place Preference Stephanie Willis, Jonnique Adjmul, Shabaaz Sandhu, Antoniette M. Maldonado-Devincci, Cheryl Kirsten ABSTRACT The present
More informationThe Biology of Addiction
The Biology of Addiction Risk factors for addiction: Biological/Genetic Family history of addiction Being male Having mental illness Exposure to substances in utero * The genes that people are born with
More informationTreatment of alcohol addiction with high-dose Baclofen. A randomised and placebo-controlled study (BACLAD) (European Neuropsychopharmacology, 2015)
Treatment of alcohol addiction with high-dose Baclofen. A randomised and placebo-controlled study (BACLAD) (European Neuropsychopharmacology, 2015) Authors: Christian A. Müller, Olga Geisel, Patricia Pelz,
More informationConditioned taste aversion produced by the oral ingestion of ethanol in the rat
Physiological Psychology 1975, Vol. 3 (4),3]7.321 Conditioned taste aversion produced by the oral ingestion of ethanol in the rat MICHAEL J. ECKARDT University of Oregon Health Sciences Center, Portland,
More informationGuilt Suicidality. Depression Co-Occurs with Medical Illness The rate of major depression among those with medical illness is significant.
1-800-PSYCH If you are obsessive-compulsive, dial 1 repeatedly If you are paranoid-delusional, dial 2 and wait, your call is being traced If you are schizophrenic, a little voice will tell you what number
More informationChapter 4. Psychopharmacology. Copyright Allyn & Bacon 2004
Chapter 4 Psychopharmacology This multimedia product and its contents are protected under copyright law. The following are prohibited by law: any public performance or display, including transmission of
More informationTO BE MOTIVATED IS TO HAVE AN INCREASE IN DOPAMINE. The statement to be motivated is to have an increase in dopamine implies that an increase in
1 NAME COURSE TITLE 2 TO BE MOTIVATED IS TO HAVE AN INCREASE IN DOPAMINE The statement to be motivated is to have an increase in dopamine implies that an increase in dopamine neurotransmitter, up-regulation
More informationNeurobiology of addiction and why it is important
Neurobiology of addiction and why it is important Stephen Jurd University of Sydney 2016 IF Addiction has a neurobiological basis THEN we should be able to: Define addiction AND Identify relevant neurological
More informationAt a Glance. Background Information. Lesson 3 Drugs Change the Way Neurons Communicate
Lesson 3 Drugs Change the Way Neurons Communicate Overview Students build upon their understanding of neurotransmission by learning how different drugs of abuse disrupt communication between neurons. Students
More informationBiological Addictions Treatment. Psychology 470. Many Types of Approaches
Many Types of Approaches Biological Addictions Treatment Psychology 470 Introduction to Chemical Additions Steven E. Meier, Ph.D. Listen to the audio lecture while viewing these slides Detoxification approaches
More informationSerotonin System May Have Potential as a Target for Cocaine Medications
NIDA - Publications - NIDA Notes - Vol. 21, No. 3 - Research Findings of 4 http://www.drugabuse.gov/nida_notes/nnvol21n3/serotonin.html 9/26/2011 3:45 PM NIDA NEWS NIDA Home > Publications > NIDA Notes
More informationRepeated stress exposure causes strain-dependent shifts in the behavioral economics of cocaine in rats
bs_bs_banneraddiction Biology PRECLINICAL STUDY doi:10.1111/adb.12123 Repeated stress exposure causes strain-dependent shifts in the behavioral economics of cocaine in rats Peter A. Groblewski 1, Chad
More informationGABAergic Influences Increase Ingestion across All Taste Categories. Liz Miller. Molly McGinnis. Lindsey Richardson
GABAergic Influences Increase Ingestion across All Taste Categories Liz Miller Molly McGinnis Lindsey Richardson A research thesis submitted in partial completion of PSY451 senior research thesis, at Wofford
More informationDr. Oslin receives grant support from the NIH, VA, and the Pennsylvania Department of Aging.
David W. Oslin, MD University of Pennsylvania Philadelphia VAMC Dr. Oslin receives grant support from the NIH, VA, and the Pennsylvania Department of Aging. Dr. Oslin is a consultant to the Hazelden Betty
More informationLOW DOSE OF ETHANOL INDUCES CONDITIONED PLACE PREFERENCE IN RATS AFTER REPEATED EXPOSURES TO ETHANOL OR SALINE INJECTIONS
Alcohol < Alcoholism Vol. 31, No. 6, pp. 547-553, 1996 LOW DOSE OF ETHANOL INDUCES CONDITIONED PLACE PREFERENCE IN RATS AFTER REPEATED EXPOSURES TO ETHANOL OR SALINE INJECTIONS PRZEMYSLAW BIENKOWSKI 12,
More informationTHE ROLE OF CORTICOTROPIN-RELEASING FACTOR (CRF) SIGNALING IN THE VENTRAL TEGMENTAL AREA IN THE REGULATION OF BINGE-LIKE ALCOHOL CONSUMPTION
Gulati 1 THE ROLE OF CORTICOTROPIN-RELEASING FACTOR (CRF) SIGNALING IN THE VENTRAL TEGMENTAL AREA IN THE REGULATION OF BINGE-LIKE ALCOHOL CONSUMPTION Varun Gulati A thesis submitted to the faculty at the
More informationIMPLICATIONS OF ENDOGENOUS OPIOIDS AND DOPAMINE IN ALCOHOLISM: HUMAN AND BASIC SCIENCE STUDIES
Alcohol & Alcoholism, Vol. 31, Suppl. 1, pp. 33-42, 1996 IMPLICATIONS OF ENDOGENOUS OPIOIDS AND DOPAMINE IN ALCOHOLISM: HUMAN AND BASIC SCIENCE STUDIES CHRISTINA GIANOULAKIS* Departments of Psychiatry
More informationPHARMACODYNAMICS OF ANTIDEPRESSANTS MOOD STABILIZING AGENTS ANXIOLYTICS SEDATIVE-HYPNOTICS
PHARMACODYNAMICS OF ANTIDEPRESSANTS MOOD STABILIZING AGENTS ANXIOLYTICS SEDATIVE-HYPNOTICS Yogesh Dwivedi, Ph.D. Assistant Professor of Psychiatry and Pharmacology Psychiatric Institute Department of Psychiatry
More informationThe study of drugs. Pharmacology
The study of drugs Pharmacology Psychopharmacology The study of psychoactive drugs Psychoactive drugs Drugs that influence psychological processes mood emotion perception cognition behavior Psychoactive
More informationAdolescent Prozac Exposure Enhances Sensitivity to Cocaine in Adulthood INTRODUCTION
INTRODUCTION Epidemiologic reports indicate that mood disorders in children and adolescents are quite common, with up to 70% of depressed children and adolescents experiencing a recurrence within 5 years
More informationPharmacotherapy of Substance Use Disorders in Children and Adolescents: Special Considerations
Pharmacotherapy of Substance Use Disorders in Children and Adolescents: Special Considerations Dr. Ajeet Sidana Department of Psychiatry Government Medical College & Hospital Chandigarh Scope of Presentation
More informationPharmacotherapy of Alcohol Use Disorders
Pharmacotherapy of Alcohol Use Disorders Roger D. Weiss, MD Professor of Psychiatry, Harvard Medical School Chief, Division of Alcohol and Drug Abuse McLean Hospital rweiss@mclean.harvard.edu Consultant
More informationPreclinical Psychopharmacology: From Mechanisms & Molecules to Medicines
Preclinical Psychopharmacology: From Mechanisms & Molecules to Medicines Pradeep G. Bhide, Ph.D. Rodgers Eminent Scholar Chair of Developmental Neuroscience Director, Center for Brain Repair Florida State
More informationWEIGHT LOSS/MANAGEMENT IS IT JUST ANOTHER PIPE DREAM?
WEIGHT LOSS/MANAGEMENT IS IT JUST ANOTHER PIPE DREAM? THE OBESITY MEDICINE ASSOCIATION S DEFINITION OF OBESITY Obesity is defined as a chronic, relapsing, multi-factorial, neurobehavioral disease, wherein
More informationDRUGS AND SOCIETY. Behavioral Medicines and Abusabie Drugs. Arthur P. Leccese, Ph.D. Kenyon College. PRENTICE HALL, Englewood Cliffs, New Jersey 07632
DRUGS AND SOCIETY Behavioral Medicines and Abusabie Drugs Arthur P. Leccese, Ph.D. Kenyon College PRENTICE HALL, Englewood Cliffs, New Jersey 07632 CONTENTS PREFACE xv PART A PSYCHOPHARMACOLOGY CHAPTER
More informationCOMBINED THERAPY: WHAT DOES ACAMPROSATE AND NALTREXONE COMBINATION TELL US?
Alcohol and Alcoholism Advance Access published September 29, 2004 Alcohol & Alcoholism Page 1 of 6 doi:10.1093/alcalc/agh093, available online at www.alcalc.oupjournals.org COMBINED THERAPY: WHAT DOES
More informationTianeptine Dependence: A Case Report
CASE REPORT Tianeptine Dependence: A Case Report Syed Nabil, Ng Chong Guan, Rusdi Abd Rashid Department of Psychological Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Abstract
More informationAlcohol: Its effects on the brain and implications for future treatment. Dr Mark Daglish
Alcohol: Its effects on the brain and implications for future treatment Senior Lecturer in Addiction Psychiatry University of Queensland Dr Mark Daglish Director of Addiction Psychiatry Royal Brisbane
More informationNeurobiology of Addiction
Neurobiology of Addiction Tiffany Love, Ph.D. Department of Psychiatry The University of Utah What is Addiction? Addiction is a chronic, relapsing, and treatable brain disorder. Compulsive drug seeking
More informationEffects of lesions of the nucleus accumbens core and shell on response-specific Pavlovian i n s t ru mental transfer
Effects of lesions of the nucleus accumbens core and shell on response-specific Pavlovian i n s t ru mental transfer RN Cardinal, JA Parkinson *, TW Robbins, A Dickinson, BJ Everitt Departments of Experimental
More informationEffects of Repeated Alcohol Deprivations on Operant Ethanol Self-Administration by Alcohol-Preferring (P) Rats
(3) 28, 1614 1621 & 3 Nature Publishing Group All rights reserved 0893-133X/03 $25.00 www.neuropsychopharmacology.org Effects of Repeated Alcohol Deprivations on Operant Ethanol Self-Administration by
More informationPharmacotherapy for Substance Use Disorders
Pharmacotherapy for Substance Use Disorders Vanessa de la Cruz, MD Chief of Psychiatry Mental Health and Substance Abuse Services Santa Cruz County Health Services Agency 1400 Emeline Avenue Santa Cruz,
More informationNaltrexone is an opioid receptor antagonist that reduces
Review Article The Status of Naltrexone in the Treatment of Alcohol Dependence Specific Effects on Heavy Drinking Helen M. Pettinati, PhD,* Charles P. O Brien, MD, PhD,*y Amanda R. Rabinowitz, BA,* Shoshana
More informationNovel Compounds for Treatment of Alcohol Addiction and Anxiety
Novel Compounds for Treatment of Alcohol Addiction and Anxiety (OTT ID 1147) Inventors: James Cook, Ph.D.; Michael Van Linn, Ph.D.; Wenyuan Yin, Ph.D. Department of Chemistry and Biochemistry UW-Milwaukee
More informationUsing Neuroimaging to Explore Addiction in Animal Models
Using Neuroimaging to Explore Addiction in Animal Models NHPs in neuroimaging can be used for Radiotracer development / Occupancy studies Modeling human drug addiction and other brain diseases Radiotracer
More informationTreatment of Alcoholism in the United States. Evidence-Based Treatment of Alcohol Use Disorder: A Focused Examination of Naltrexone s Role
Treatment of Alcoholism in the United States Evidence-Based Treatment of Alcohol Use Disorder: A Focused Examination of s Role Charles P. O Brien, MD, PhD Professor of Psychiatry University of Pennsylvania
More informationEffects of Alprazolam and Fluoxetine on Morphine Sensitization in Mice
Physiol. Res. 51: 417-423, 2002 Effects of Alprazolam and Fluoxetine on Sensitization in Mice M. VOTAVA, M. KRŠIAK, V. MORAVEC Department of Pharmacology, Third Faculty of Medicine, Charles University,
More informationJames M. Murphy, Ting-Kai Li, Lawrence Lumeng and William J. McBride
JPET Fast This article Forward. has not been Published copyedited on and August formatted. 2, The 2005 final version as DOI:10.1124/jpet.105.084350 may differ from this version. JPET #84350 1 Prolonged
More informationThaddeus Ulzen MD FRCP(C)FAPA FCGP Professor & Chair, Department of Psychiatry and Behavioral Medicine, Associate Dean for Academic Affairs
Thaddeus Ulzen MD FRCP(C)FAPA FCGP Professor & Chair, Department of Psychiatry and Behavioral Medicine, Associate Dean for Academic Affairs CCHS/University of Alabama School of Medicine Assessment History
More informationCouncil on Chemical Abuse Annual Conference November 2, The Science of Addiction: Rewiring the Brain
Council on Chemical Abuse Annual Conference November 2, 2017 The Science of Addiction: Rewiring the Brain David Reyher, MSW, CAADC Behavioral Health Program Director Alvernia University Defining Addiction
More informationVOLUME C. Pharmacological Treatment for Drug Use Disorders Drug Treatment for Special Populations
VOLUME C Pharmacological Treatment for Drug Use Disorders Drug Treatment for Special Populations Module 2 Basics of opioid dependence Pharmacotherapy options Opioids: Definition, effects and treatment
More informationStart Low, Go Slow but Treat to Target
Start Low, Go Slow but Treat to Target Pharmacotherapy for Depression, Anxiety and At-Risk Alcohol Use in Late Life September 29, 2014 Audio and Control Panel instruction On the phone? Raise your hand
More informationDoes nicotine alter what is learned about non-drug incentives?
East Tennessee State University Digital Commons @ East Tennessee State University Undergraduate Honors Theses 5-2014 Does nicotine alter what is learned about non-drug incentives? Tarra L. Baker Follow
More informationThe Sinclair Method (TSM) for the Treatment of Alcoholism. Clinical Research Findings and Best Protocol for Success Updated 2014
Information for Medical & Treatment Professionals The Sinclair Method (TSM) for the Treatment of Alcoholism Clinical Research Findings and Best Protocol for Success Updated 2014 "One medication, naltrexone,
More informationOrientation for New Child and Adolescent Psychiatry Residents: Module Four Pediatric Psychopharmacology
Orientation for New Child and Adolescent Psychiatry Residents: Module Four Pediatric Psychopharmacology Objective: To discuss basic principles of psychopharmacology in children and adolescents. Pharmacokinetics:
More informationPSY 302 Lecture 6: The Neurotransmitters (continued) September 12, 2017 Notes by: Desiree Acetylcholine (ACh) CoA + Acetate Acetyl-CoA (mitochondria) (food, vinegar) + Choline ChAT CoA + ACh (lipids, foods)
More informationSerotonergic mechanisms of MDMA self-administration. Susan Schenk Victoria University of Wellington School of Psychology
Serotonergic mechanisms of MDMA self-administration Susan Schenk Victoria University of Wellington School of Psychology My lab works in the broad area of Behavioural Pharmacology We test the effects of
More informationGeneral introduction. Chapter 1
General introduction Chapter 1 General introduction Historical aspects of drug use Religious, medicinal and recreational use of mind-altering substances by humans has a history of thousands of years 1.
More informationHISTAMINE INHIBITS EATING WITHOUT ALTERING POSTPRANDIAL SATIETY IN RATS KELLY TSCHANTZ
HISTAMINE INHIBITS EATING WITHOUT ALTERING POSTPRANDIAL SATIETY IN RATS KELLY TSCHANTZ Abstract Exogenous histamine decreases food intake and injection of H-1 antagonists increases food intake in rats.
More informationWhat are Substance Use Disorders?
What are Substance Use Disorders? Sanchit Maruti, MD Michael Goedde, MD University of Vermont Medical Center 1 Disclosures } Drs. Maruti and Goedde receive compensation as consultants to the American Academy
More informationClasses of Neurotransmitters. Neurotransmitters
1 Drugs Outline 2 Neurotransmitters Agonists and Antagonists Cocaine & other dopamine agonists Alcohol & its effects / Marijuana & its effects Synthetic & Designer Drugs: Ecstasy 1 Classes of Neurotransmitters
More informationC81ADD Psychology of Addiction. Alcohol. Ethyl alcohol (ethanol) School of Psychology. Tobias Bast.
C81ADD Psychology of Addiction Alcohol Ethyl alcohol (ethanol) Tobias Bast School of Psychology tobias.bast@nottingham.ac.uk 1 Selected aspects of the psychopharmacology of alcohol (ethanol) Primary neuropharmacological
More informationDisclosure Information I have the following financial relationships to disclose:
Gambling and Other Addictive Disorders Jon E. Grant, JD, MD, MPH Professor University of Chicago Disclosure Information I have the following financial relationships to disclose: My research is supported
More informationFinal Exam PSYC2022. Fall (1 point) True or False. The DSM-IV describes the symptoms of acute intoxication with cannabis.
Final Exam PSYC2022 Fall 1998 (2 points) Give 2 reasons why it is important for psychological disorders to be accurately diagnosed. (1 point) True or False. The DSM-IV describes the symptoms of acute intoxication
More informationBRAIN MECHANISMS OF REWARD AND ADDICTION
BRAIN MECHANISMS OF REWARD AND ADDICTION TREVOR.W. ROBBINS Department of Experimental Psychology, University of Cambridge Many drugs of abuse, including stimulants such as amphetamine and cocaine, opiates
More informationThe Neurobiology of Mood Disorders
The Neurobiology of Mood Disorders J. John Mann, MD Professor of Psychiatry and Radiology Columbia University Chief, Department of Neuroscience, New York State Psychiatric Institute Mood Disorders are
More informationReview of potential pharmacotherapies and their scientific basis
Choosing Pharmacotherapies for the COMBINE Study- Process and Procedures: An Investigational Approach to Combination Pharmacotherapy for the Treatment of Alcohol Dependence* ROBERT SWIFT, M.D., PH.D.,"
More informationIntroduction ORIGINAL INVESTIGATION
Psychopharmacology (2001) 155:27 34 DOI 10.1007/s002130000629 ORIGINAL INVESTIGATION Kent E. Hutchison Robert Swift Damaris J. Rohsenow Peter M. Monti Dena Davidson Alissa Almeida Olanzapine reduces urge
More informationThe Nervous System. Chapter 4. Neuron 3/9/ Components of the Nervous System
Chapter 4 The Nervous System 1. Components of the Nervous System a. Nerve cells (neurons) Analyze and transmit information Over 100 billion neurons in system Four defined regions Cell body Dendrites Axon
More informationNaltrexone reduces ethanol- and sucrose-reinforced responding in rhesus monkeys
Psychopharmacology (1998) 139:53 61 Springer-Verlag 1998 ORIGINAL INVESTIGATION Keith L. Williams Gail Winger Eric D. Pakarinen James H. Woods Naltrexone reduces ethanol- and sucrose-reinforced responding
More informationOverview of Potential Treatment Medications for Cocaine Dependence
Overview of Potential Treatment Medications for Cocaine Dependence Elinore F. McCance INTRODUCTION The search for a pharmacotherapeutic agent for the treatment of cocaine dependence began in the early
More informationIf gambling treatment was evidence based, what would it look like?
If gambling treatment was evidence based, what would it look like? Professor Mark Griffiths International Gaming Research Unit Nottingham Trent University E-mail : mark.griffiths@ntu.ac.uk Website :http://ess.ntu.ac.uk/griffiths
More informationWashtenaw Community College Comprehensive Report. PSY 296 Neuropsychology of Addiction Effective Term: Winter 2019
Washtenaw Community College Comprehensive Report PSY 296 Neuropsychology of Addiction Effective Term: Winter 2019 Course Cover Division: Humanities, Social and Behavioral Sciences Department: Behavioral
More informationStudy Guide Unit 3 Psych 2022, Fall 2003
Psychological Disorders: General Study Guide Unit 3 Psych 2022, Fall 2003 1. What are psychological disorders? 2. What was the main treatment for some psychological disorders prior to the 1950 s? 3. What
More informationA brain microdialysis study on 5-HT release in freely moving rat lines selectively bred for differential 5-HT 1A receptor function
Brazilian Journal of Medical and Biological Research (3) 36: 63-67 Serotonin and 5-HT 1A rat lines ISSN 1-879X 63 A brain microdialysis study on 5-HT release in freely moving rat lines selectively bred
More informationEffects of Caffeine on Memory in Rats
Western University Scholarship@Western 2015 Undergraduate Awards The Undergraduate Awards 2015 Effects of Caffeine on Memory in Rats Cisse Nakeyar Western University, cnakeyar@uwo.ca Follow this and additional
More informationNo! No! No! No! With the possible exception of humans Public Health Question Does the compound have the potential to be abused? Public Health Question Does the compound have the potential to be abused?
More informationMedical Management of Substance Use Disorders: Does research translate to clinical practice
Medical Management of Substance Use Disorders: Does research translate to clinical practice Ashwin A Patkar, MD Professor of Psychiatry & Community & Family Medicine Duke University Medical Center Durham,
More informationVarenicline and Other Pharmacotherapies for Tobacco Dependence
Varenicline and Other Pharmacotherapies for Tobacco Dependence J. Taylor Hays, M.D. Associate Director Nicotine Dependence Center Mayo Clinic 2012 MFMER slide-1 Learning Objectives Understand the mechanism
More informationFlavor avoidance learning based on missing calories but not on palatability reduction
Learn Behav (212) 4:542 55 DOI.3758/s1342-12-74-6 Flavor avoidance learning based on missing calories but not on palatability reduction Robert A. Boakes & Angela E. Patterson & Dorothy W. S. Kwok Published
More informationAlcohol Antagonists 1
Alcohol Antagonists 1 What is an alcohol antagonist? An alcohol antagonist is a drug that specifically blocks the effects of alcohol. If you take an alcohol antagonist and then drink a bunch of alcohol,
More informationMany substances that relay signals among neurons
tration triggers the release of neurotransmitter molecules into the synaptic cleft. Two large groups of receptors exist that elicit specific responses in the receptor cell: Receptors that act as ligandgated
More informationUnderstanding Addiction and Its Impact on the Brain. SDSMA Webinar Matthew Stanley, DO
Understanding Addiction and Its Impact on the Brain SDSMA Webinar Matthew Stanley, DO Estimated Economic Cost to Society Due to Substance Abuse and Addiction: Illegal drugs: Alcohol: Tobacco: $181 billion/year
More informationEvidence-Based Treatment Approaches for Gambling Disorder
Evidence-Based Treatment Approaches for Gambling Disorder Jon E. Grant, JD, MD, MPH Professor University of Chicago Pritzker School of Medicine Chicago, IL 6/8/2016 Disclosure Information My research is
More informationThe Reduction of the Demand of Nicotine Due to Pregabalin and Gabapentin: Two Cases ME Ceylan 1, A Evrensel 1, BÖ Ünsalver 1, G Cömert 2 ABSTRACT
The Reduction of the Demand of Nicotine Due to Pregabalin and Gabapentin: Two Cases ME Ceylan 1, A Evrensel 1, BÖ Ünsalver 1, G Cömert 2 ABSTRACT Pregabalin and gabapentin, it s pharmacological like drug
More informationNeuroscience of Addiction
Neuroscience of Addiction Carlton Erickson, Ph.D. Associate Dean for Research and Graduate Studies Distinguished Professor of Pharmacology Director, Addiction Science Research and Education Center College
More information- Neurotransmitters Of The Brain -
- Neurotransmitters Of The Brain - INTRODUCTION Synapsis: a specialized connection between two neurons that permits the transmission of signals in a one-way fashion (presynaptic postsynaptic). Types of
More information