Differential Effects of Oxycodone, Hydrocodone, and Morphine on Activation Levels of Signaling Molecules
|
|
- Kathryn Payne
- 6 years ago
- Views:
Transcription
1 Pain Medicine 2016; 17: doi: /pme Brief Research Report Differential Effects of Oxycodone, Hydrocodone, and Morphine on Activation Levels of Signaling Molecules Michael A. Emery, BA, M. L. Shawn Bates, MA, Paul J. Wellman, PhD, and Shoshana Eitan, PhD Department of Psychology, Behavioral and Cellular Neuroscience Program, and the Interdisciplinary Program in Neuroscience, Texas A&M Institute for Neuroscience (TAMIN), Texas A&M University, College Station, Texas, USA Correspondence to: Shoshana Eitan, PhD, Department of Psychology, Texas A&M University, 4235 TAMU, College Station, TX 77843, USA. Tel: ; Fax: ; Funding sources: M.A.E. and M.L.S.B. were supported by the Heep fellowship in Neuroscience awarded by the Texas A&M Institute for Neuroscience (TAMIN). This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Disclosure and conflicts of interest: The authors have no financial interests to disclose. Abstract Background. Opioids alter the responses of D2-like dopamine receptors (D2DRs), known to be involved in the pathology of addiction and other mental illnesses. Importantly, our recent results demonstrated that various opioids differentially modulate the behavioral responses of D2DRs. Objective. To examine the effect of various opioids on striatal activation levels of Akt and ERK1/2, as well as the signaling responses of D2DRs following opioid exposure. Methods. Mice were pre-treated with 20 mg/kg morphine, hydrocodone, oxycodone, or saline for 6 days. Twenty-four hours later, mice were injected with vehicle or a D2/D3 receptor agonist, quinpirole. Thirty minutes later, dorsal striatum was collected and analyzed using Western blot. Results. In morphine-pretreated animals, baseline Akt activation level was unchanged, but was reduced in response to quinpirole. In contrast, baseline Akt activation levels were reduced in mice pretreated with hydrocodone and oxycodone, but were unchanged in response to quinpirole. In mice pretreated with all opioids, baseline ERK2 activation levels were unchanged and increased in response to quinpirole. However, quinpiroleinduced ERK2 activation was significantly higher than drug naïve animals only in the morphine-pretreated mice. Conclusions. Various opioids differentially modulate the baseline activation levels of signaling molecules, which in turn results in ligand-selective effects on the responses to a D2/D3 dopamine receptor agonist. This demonstrates a complex interplay between opioid receptors and D2DRs, and supports the notion that various opioids carry differential risks to the dopamine reward system. This information should be considered when prescribing opioid pain medication, to balance effectiveness with minimal risk. Key Words. Opioid; Pain Management; Addiction; Abuse; Akt; ERK1/2 Introduction Opioids are widely used for the management of moderate-to-severe pain and are commonly misused and abused. Exposure to opioid analgesics has been associated with altered responses of D2-like dopamine receptors (D2DRs) [1 5]. Our previous studies demonstrated that various opioids modulate the responses of D2DRs in differential degrees. Specifically, mice administered methadone in clinically relevant doses demonstrated significantly greater locomotor supersensitivity to quinpirole, a D2/D3 receptor agonist, than drug-naïve mice. However, mice administered buprenorphine did not, even at super- VC 2015 American Academy of Pain Medicine. All rights reserved. For permissions, please journals.permissions@oup.com 908
2 Differential Effects of Opioids on Signaling therapeutic doses [6]. Moreover, mice pretreated with oxycodone showed significantly greater locomotor supersensitivity to quinpirole than did mice pretreated with equianalgesic doses of morphine, while mice pretreated with equianalgesic doses of hydrocodone showed sensitivity between that of mice treated with morphine and oxycodone [7]. Disturbances in the responses of the D2DRs would be expected to have important implications for the abuse potential of opioids and other drugs of abuse. The D2DRs are known to be involved in the reinforcing properties of morphine [8], and in mediating drug-seeking behaviors in mice [9] and rats [10] undergoing morphine withdrawal. Specifically, the D2L splice variant of the receptor was demonstrated to be essential for the rewarding properties of morphine [11,12]. In addition, an association has been observed between D2 receptor genes and the abuse of various illicit drugs, as well as between D2 receptor genes and alcoholism [13 15]. Moreover, the D2DRs were also suggested to be involved in the pathophysiology of affective and psychotic disorders [16 18]. Opioid receptors and D2DRs are known to signal via changes in the activation levels (i.e., phosphorylation levels) of both extracellular-signal-regulated kinases (ERKs) 1 and 2, also known as p44/p42 mitogen-activated protein kinase (MAPK) [19 23], and Akt, also known as protein kinase B (PKB) [24 26]. Thus, in the present study, we examined the differential effects of repeated administration of oxycodone, hydrocodone, and morphine on the activation/phosphorylation levels of Akt and ERK1/2. Additionally, we examined the differential effects of repeated administration of oxycodone, hydrocodone, and morphine on altering the signaling responses to quinpirole, a D2/D3 dopamine receptor agonist. We used equianalgesic oral doses of oxycodone, hydrocodone, and morphine that were previously established to provide equianalgesia [7]. As in our previous studies, the oral route was chosen to provide a more accurate and realistic translational model of human administration of oxycodone and hydrocodone and abuse of these prescription opioid medications. Methods Animals All animal procedures were conducted in accordance with the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals, and were approved by the Texas A&M Institutional Animal Care and Use Committee. Male C57BL/6 mice, purchased from Harlan Laboratories (Houston, TX) were housed 3 5 per cage with food and water ad libitum. They were acclimated to the temperature-controlled ( C) vivarium with a 12 hour/12 hour light/dark cycle (lights on at 07:00) for 5 7 days prior to the start of experiments. Mice were treated and tested from postnatal day (PND) 27 35, because previous studies indicate that the effect on D2DR responses is more pronounced at these ages [27,28]. Drugs Mice were administered oxycodone, hydrocodone, morphine (20 mg/kg, 10 ml/kg) or saline (10 ml/kg) once daily (9 AM) for six days via gavage. Drugs were purchased from Sigma-Aldrich Chemicals (St. Louis, MO). These doses represent base plus salt concentrations. For oxycodone these doses roughly correspond to 18 mg/kg base. For hydrocodone, these doses roughly correspond to 13 mg/kg base. For morphine, these doses roughly correspond to 15 mg/kg base. These doses were selected to represent equianalgesic doses as was confirmed by tail withdrawal test in our previous study [7]. Please note that there are species- and agedependent differences in the pharmacokinetics of opioids (absorbance, metabolism, etc.), as well as in the levels and distribution of opioid receptors, which are likely involved in the underlying response for these oral doses to represent equianalgesic doses. Experimental Design Mice (n ¼ 9 14 per group) were pre-treated with morphine, hydrocodone, oxycodone (20 mg/kg, 10 ml/kg) or saline (10 ml/kg) via gavage once daily for 6 days. Twenty-four hours following the final opioid/saline administration, mice were injected with quinpirole hydrochloride (10 mg/kg, 10 ml/kg, i.p.) or vehicle (100 mm hydrochloric acid, 10 ml/kg). Thirty minutes following quinpirole/vehicle injection, mice were deeply anesthetized with sodium pentobarbital (120 mg/kg, 10 ml/kg), brains were extracted, and flash-frozen in a bath of 2- methylbutane cooled on dry ice. Dorsal striatum tissue was dissected out of the flash-frozen brains and stored at 80 C until processed for Western blot. The number of animals in each experiment group was as follows: Saline-Vehicle n ¼ 10; Saline-Quinpirole n ¼ 9; Morphine-Vehicle n ¼ 9; Morphine-Quinpirole n ¼ 14; Hydrocodone-Vehicle n ¼ 9; Hydrocodone-Quinpirole n ¼ 11; Oxycodone-Vehicle n ¼ 9; Oxycodone-Quinpirole n ¼ 10. Western Blots Striatum tissue was homogenized in boiling 1% SDS plus 2 mm okadaic acid. Homogenized samples were then boiled for 10 minutes. Total protein concentration was determined for each sample using DC Protein Assay (Bio-Rad). Samples were diluted to 200 mg total protein in loading buffer and boiled for an additional 10 minutes. Samples were then loaded and resolved on 10% SDS-PAGE then transferred to PVDF membrane. Blots were probed using antibodies to p-p44/42 MAPK (perk) (T202/Y204, 1:1,000, Cell Signaling Technology), P44/42 MAPK (Total ERK) (1:1,000, Cell Signaling Technology), pakt (S473, 1:1,000, Cell Signaling Technology), and Akt (total Akt) (1:1,000, Cell Signaling Technology). Membranes were then incubated with 909
3 Emery et al. HRP-conjugated secondary antibody (1:5,000, Bio- Rad), developed with ECL, and imaged using AlphaView software (Cell Biosciences). Phospho-protein signals were normalized to total protein signals on the same membrane. Data Analysis For each mouse s striatum, the ratio of phospho-protein:total protein was calculated for Akt, ERK1, and ERK2, and expressed as a percentage. For each experimental group, the percent change was averaged for each protein. Data for the between-subjects factors of pretreatment (morphine, hydrocodone, oxycodone, or saline) and treatment (quinpirole vs vehicle) were analyzed using two-way ANOVA. Post hoc contrasts between each treatment group were computed using Bonferroni procedure. Differences with P-values of less than 0.05 were deemed statistically significant. Results are presented as mean 6 SEM. Results Akt Two-way ANOVA revealed a main effect of pretreatment with the various opioids (F[3, 71] ¼ 16.73, P < ), a main effect of treatment with quinpirole (F[1, 71] ¼ 24.20, P < ), and a significant interaction between pretreatment and quinpirole treatment (F[3, 71] ¼ 4.10, P < 0.01). Bonferroni post hoc comparison revealed that morphine pretreatment did not alter Akt activation levels (i.e., phospho-akt/total Akt) in the dorsal striatum as compared to levels observed in drugnaïve animals (P > 0.05, n.s.). In contrast, pretreatment with both oxycodone and hydrocodone significantly decreased Akt activation levels in the dorsal striatum (P < 0.001) (Figure 1). Additionally, differential responses to quinpirole were also observed in mice pretreated with various opioids. Quinpirole administration did not significantly alter Akt activation levels in drug naïve animals (P > 0.05, n.s.). In contrast, quinpirole administration reduced Akt activation levels in morphine pretreated animals (P < 0.001). However, no further reduction in Akt activation levels (from baseline) was observed in mice pretreated with hydrocodone or oxycodone in response to quinpirole (P > 0.05, n.s.). ERK1/p44 MAPK Two-way ANOVA revealed a main effect of pretreatment with the various opioids (F[3, 73] ¼ 3.02, P < 0.05). However, there was no main effect of treatment with quinpirole (F[1, 73] ¼ 1.24, P > 0.05), and no significant interaction between pretreatment and quinpirole treatment (F[3, 73] ¼ 0.89, P > 0.05). Bonferroni post hoc comparison revealed that opioid pretreatment did not significantly alter ERK1 activation levels (i.e., phospho- ERK1/total ERK1) in the dorsal striatum as compared to levels observed in drug-naïve animals (P > 0.05, n.s.). Additionally, quinpirole administration did not significantly alter ERK1 activation levels in either the drugnaïve or in the opioid-pretreated animals (P > 0.05, n.s.) (Figure 2). ERK2/p42 MAPK Two-way ANOVA revealed a main effect of pretreatment with the various opioids (F[3, 73] ¼ 10.86, P < ), a Figure 1 Effects of opioid pretreatment on Akt activation (phosphorylation) levels within dorsal striatum and differential responses to quinpirole. Phosphorylation of Akt in the dorsal striatum 30 minutes following vehicle or quinpirole injection, graphed as a percentage of total protein level. *indicates significant difference (P < 0.05) from same pre-treatment vehicle controls. indicates significant difference (P < 0.05) from saline pre-treated animals. Data presented as mean 6 SEM. Figure 2 Effects of opioid pretreatment on ERK1/2 activation (phosphorylation) levels within dorsal striatum and differential responses to quinpirole. Phosphorylation of ERK1/2 in the dorsal striatum 30 minutes following vehicle or quinpirole injection, graphed as a percentage of total protein level. *indicates significant difference (P < 0.05) from same pre-treatment vehicle controls. indicates significant difference (P < 0.05) from saline pre-treated animals. Data presented as mean 6 SEM. 910
4 Differential Effects of Opioids on Signaling main effect of treatment with quinpirole (F[1, 73] ¼ 27.04, P < ), but no significant interaction between pretreatment and quinpirole treatment (F[3, 73] ¼ 1.21, P > 0.05). Bonferroni post hoc comparison revealed that opioid pretreatment did not alter ERK2 activation levels (i.e., phospho-erk2/total ERK2) in the dorsal striatum as compared to levels observed in drugnaïve animals (P > 0.05, n.s.). Although visually there seems to be a tendency towards increased ERK2 activation levels in morphine-pretreated animals, and a tendency towards decreased ERK2 activation levels following oxycodone pretreatment, nonetheless even a statistical trend was not observed. Quinpirole administration did not significantly alter ERK2 activation levels in drug naïve animals (P > 0.05, n.s.). In contrast, increased ERK2 activation in response to quinpirole was observed in mice pretreated with opioids (P < 0.05). However, ERK2 activation level was significantly higher than drug naïve animals following quinpirole only in the morphine-pretreated mice (P < 0.001). Discussion In the current study, we observed that pretreatment with equianalgesic doses of oxycodone, hydrocodone, and morphine results in differential patterns of phosphorylation (activation) of the cellular signaling proteins Akt and ERK1/2. Moreover, pretreatment with these opioids have differential effects on the signaling responses to quinpirole, a D2/D3 receptor agonist. These findings suggest a complex interplay of signaling between opioid receptors and D2DRs within the striatum, and provide further evidence supporting the notion that various opioids carry differential risks to the dopamine reward system. Various opioids display differential affinities to the three opioid receptors, m-, d-, and j-opioid receptor (MOR, DOR, and KOR, respectively). Specifically, while all three drugs are most selective for MOR, morphine s affinity for DOR and KOR, while lower than its affinity for MOR, is notably higher than either hydrocodone or oxycodone, which have very low affinities for DOR and KOR [29,30]. Additionally, various opioids were demonstrated to differentially modulate downstream signaling even when binding to and activating the same receptor [31 33], a phenomenon termed ligand-directed signaling or biased agonism. This is likely related to the ability of G-protein coupled receptors to signal via different mechanisms and the differential abilities of various opioids to activate those various mechanisms. These mechanisms include the canonical G-protein coupled signaling (GPCS) and the non-canonical G-protein independent signaling which involves the scaffolding proteins beta-arrestins (barr). For example, mice lacking barr2 show no development of tolerance to morphine, as well as an attenuation of naloxone-induced withdrawal [34]. These mice showed normal tolerance and withdrawal when treated with oxycodone, methadone, or fentanyl, which are known to signal via the same receptor. Different opioids have been shown to activate ERK differently [35]. Additionally, oxycodone and morphine have been demonstrated to differentially activate MOR and have differential pain relieving efficacies in various conditions [36]. Moreover, various opioids can have very different levels of side effects, despite equal potency to relieve pain [7,37]. Thus, the differential effects of the various opioids on activation levels of downstream signaling molecules might be attributed to differential effects at the various opioid receptors as well as the differential effects of various opioids on activation of GPCS and barr-dependent signaling at the same receptor. The differential modulation of activation levels of signaling molecules by various opioids are likely to account for the differential effects of various opioids on the signaling responses to a D2DR agonist. Like opioid receptors, D2DRs are G protein-coupled receptors that can signal through both GPCS and barr-dependent signaling. barr is known to be involved in the desensitization of the ability of D2DRs to signal via GPCS [38 40]. However, barr2 was also demonstrated to play a role in D2DR signaling by forming a complex that inactivates (decreases phosphorylation of) the cell signaling protein Akt [25,41,42]. This study shows that pretreatment with oxycodone or hydrocodone is accompanied by a decreased phosphorylation of Akt. However, quinpirole did not alter Akt activation state in the oxycodone- or hydrocodone-pretreated animals. This might suggest that prior treatment with oxycodone or hydrocodone decreases the ability of the D2DRs to signal via barrdependent mechanism. GPCS through D2DRs is subject to a faster desensitization rate as compared to a barr-dependent mechanism [25]. Thus, this result suggests that pretreatment with oxycodone or hydrocodone will lead to an increase in the desensitization rate of the signaling through D2DRs. Importantly, morphine did not affect Akt activation levels, which might preserve D2DRs ability to signal via barr-dependent mechanism, i.e. quinpirole inactivated Akt in morphine-pretreated mice. Moreover, the effect of quinpirole to reduce Akt phosphorylation levels was significantly enhanced in the morphine-pretreated animals as compared to drugnaïve mice. This suggests that morphine pretreatment not only did not decrease, but might have enhanced the ability of D2DRs to signal via barr, in a mechanism yet to be identified. In this study, repeated administration of opioids alone did not significantly alter phosphorylation of ERK1 or ERK2 in the dorsal striatum. Although it should be noted that a trend toward increased ERK2 activation levels was observed in morphine-pretreated animals, and a trend toward decreased ERK2 activation levels was observed following oxycodone pretreatment, neither reached statistical significance. None of the opioids, repeatedly administered followed by an acute challenge with quinpirole resulted in activation of ERK1. However, all of the opioids followed by quinpirole resulted in activation of ERK2, relative to levels seen in opioid-treated animals that were not administered 911
5 Emery et al. quinpirole. In morphine-pretreated animals, this was also increased relative to opioid-naïve protein levels following quinpirole. D2DRs were shown to activate ERK [43 45]. Activation of ERK by D2DRs was reported to be almost exclusively in a rapid, G-protein-dependent manner, that returns to baseline within 15 minutes [46,47]. However, in this study, significant activation of ERK2 was observed in morphine-pretreated mice at 30 minutes post-quinpirole. This suggests that the quinpirole-induced ERK activation observed in this study might be via a yet to be identified barr-dependent mechanism. Importantly, although quinpirole-induced ERK2 activation was also observed in oxycodone and hydrocodone pretreated animals, it was not significantly above control levels. Thus, further studies are needed to elucidate potential differences in the effect of various opioids on the abilities of D2DRs to signal via GPCS and barr. This study demonstrates that, at equianalgesic dosages, various opioids differentially alter striatal Akt and ERK activation levels in ways unique to individual opioids. These differential modulations of signaling are suggested to account for the distinct effects of various opioids on the signaling responses, as well as the locomotor response of D2DRs [7]. The general risks associated with opioid use and abuse have long been understood, and various opioids carry differing levels of efficacy and abuse potential. Here, we show differential effects of various opioids on striatal signaling molecules and the dopamine reward pathway. This information should be considered when prescribing opioid pain medication, to balance effectiveness with minimal risk. References 1 Lee JM, DeLeon-Jones F, Fields JZ, Ritzmann RF. Cyclo (Leu-Gly) attenuates the striatal dopaminergic supersensitivity induced by chronic morphine. Alcohol Drug Res 1987;7: Reddy PL, Veeranna, Thorat SN, Bhargava HN. Evidence for the behavioral supersensitivity of dopamine D2 receptors without receptor up-regulation in morphine-abstinent rats. Brain Res 1993;607: Piepponen TP, Katajamäki J, Kivastik T, Zharkovsky A, Ahtee L. Behavioural and neurochemical sensitization of morphine-withdrawn rats to quinpirole. Pharmacol Biochem Behav 1996;54: Druhan JP, Walters CL, Aston-Jones G. Behavioral activation induced by D(2)-like receptor stimulation during opiate withdrawal. J Pharmacol Exp Ther 2000;294: Hofford RS, Wellman PJ, Eitan S. Morphine alters the locomotor responses to a D2/D3 dopamine receptor agonist differentially in adolescent and adult mice. J Psychopharm 2012;26: Barwatt JW, Hofford RS, Emery MA, Bates ML, Wellman PJ, Eitan S. Differential effects of methadone and buprenorphine on the response of D2/D3 dopamine receptors in adolescent mice. Drug Alcohol Depend 2013;132: Emery MA, Bates MLS, Wellman PJ, Eitan S. Differential effects of oxycodone, hydrocodone, and morphine on the responses of D2/D3 dopamine receptors. Behav Brain Res 2015;284: Elmer GI, Pieper JO, Rubinstein M, et al. Failure of intravenous morphine to serve as an effective instrumental reinforcer in dopamine D2 receptor knockout mice. J Neurosci 2002;22:RC Dockstader CL, Rubinstein M, Grandy DK, Low MJ, van der Kooy D. The D2 receptor is critical in mediating opiate motivation only in opiate-dependent and withdrawn mice. Eur J Neurosci 2001;13: De Vries TJ, Schoffelmeer AN, Binnekade R, Vanderschuren LJ. Dopaminergic mechanisms mediating the incentive to seek cocaine and heroin following long-term withdrawal of IV drug self-administration. Psychopharmacology (Berl) 1999;143: Maldonado R, Saiardi A, Valverde O, et al. Absence of opiate rewarding effects in mice lacking dopamine D2 receptors. Nature 1997;388: Smith JW, Fetsko LA, Xu R, Wang Y. Dopamine D2L receptor knockout mice display deficits in positive and negative reinforcing properties of morphine and in avoidance learning. Neuroscience 2002;113: Blum K, Noble EP, Sheridan PJ, et al. Association of the A1 allele of the D2 dopamine receptor gene with severe alcoholism. Alcohol 1991;8: Nemoda Z, Szekely A, Sasvari-Szekely M. Psychopathological aspects of dopaminergic gene polymorphisms in adolescence and young adulthood. Neurosci Biobehav Rev 2011;35: Esposito-Smythers C, Spirito A, Rizzo C, McGeary JE, Knopik VS. Associations of the DRD2 TaqIA polymorphism with impulsivity and substance use: Preliminary results from a clinical sample of adolescents. Pharmacol Biochem Behav 2009;93: Seeman P. All roads to schizophrenia lead to dopamine supersensitivity and elevated dopamine D2(high) receptors. CNS Neurosci Ther 2011;17:
6 Differential Effects of Opioids on Signaling 17 Gershon AA, Vishne T, Grunhaus L. Dopamine D2- like receptors and the antidepressant response. Biol Psychiatry 2007;61: Svestka J. Treatment of bipolar depression. Neuro Endocrinol Lett 2005;26: Burt AR, Carr IC, Mullaney I, Anderson NG, Milligan G. Agonist activation of p42 and p44 mitogen-activated protein kinases following expression of the mouse delta opioid receptor in Rat-1 fibroblasts: Effects of receptor expression levels and comparisons with G-protein activation. Biochem J 1996;320: Macey TA, Lowe JD, Chavkin C. Mu opioid receptor activation of ERK1/2 is GRK3 and arrestin dependent in striatal neurons. J Biol Chem 2006;281: Eitan S, Bryant CD, Saliminejad N, et al. Brain region-specific mechanisms for acute morphineinduced mitogen-activated protein kinase modulation and distinct patterns of activation during analgesic tolerance and locomotor sensitization. J Neurosci 2003;23: Welsh GI, Hall DA, Warnes A, Strange PG, Proud CG. Activation of microtubule-associated protein kinase (Erk) and p70 S6 kinase by D2 dopamine receptors. J Neurochem 1998;70: Cai G, Zhen X, Uryu K, Friedman E. Activation of extracellular signal-regulated protein kinases is associated with a sensitized locomotor response to D(2) dopamine receptor stimulation in unilateral 6-hydroxydopamine-lesioned rats. J Neurosci 2000;20: Polakiewicz RD, Schieferl SM, Gingras AC, Sonenberg N, Comb MJ. mu-opioid receptor activates signaling pathways implicated in cell survival and translational control. J Biol Chem 1998;273: Beaulieu JM, Sotnikova TD, Marion S, et al. An Akt/ beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior. Cell 2005;122: Russo SJ, Bolanos CA, Theobald DE, et al. IRS2- Akt pathway in midbrain dopamine neurons regulates behavioral and cellular responses to opiates. Nat Neurosci 2007;10: Hofford RS, Wellman PJ, Eitan S. Morphine alters the locomotor responses to a D2/D3 dopamine receptor agonist differentially in adolescent and adult mice. J Psychopharmacol 2012;26: Spear LP, Horowitz GP, Lipovsky J. Altered behavioral responsivity to morphine during the periadolescent period in rats. Behav Brain Res 1982;4: Yoburn BC, Shah S, Chan K, Duttaroy A, Davis T. Supersensitivity to opioid analgesics following chronic opioid antagonist treatment: Relationship to receptor selectivity. Pharmacol Biochem Behav 1995;51: Peckham EM, Traynor JR. Comparison of the antinociceptive response to morphine and morphine-like compounds in male and female Sprague-Dawley rats. J Pharmacol Exp Ther 2006; 316: Pradhan AA, Smith ML, Kieffer BL, Evans CJ. Ligand-directed signalling within the opioid receptor family. Br J Pharmacol 2012;167: Kelly E, Bailey CP, Henderson G. Agonist-selective mechanisms of GPCR desensitization. Br J Pharmacol 2008;153:S Evans CJ. Secrets of the opium poppy revealed. Neuropharmacology 2004;47: Raehal KM, Bohn LM. The role of beta-arrestin2 in the severity of antinociceptive tolerance and physical dependence induced by different opioid pain therapeutics. Neuropharmacology 2011;60: Zheng H, Loh HH, Law PY. Beta-arrestin-dependent mu-opioid receptor-activated extracellular signalregulated kinases (ERKs) Translocate to Nucleus in Contrast to G protein-dependent ERK activation. Mol Pharmacol 2008;73: Nakamura A, Hasegawa M, Minami K, et al. Differential activation of the mu-opioid receptor by oxycodone and morphine in pain-related brain regions in a bone cancer pain model. Br J Pharmacol 2013;168: Meert TF, Vermeirsch HA. A preclinical comparison between different opioids: Antinociceptive versus adverse effects. Pharmacol Biochem Behav 2005; 80: Luttrell LM, Lefkowitz RJ. The role of beta-arrestins in the termination and transduction of G-proteincoupled receptor signals. J Cell Sci 2002;115: Celver J, Sharma M, Thanawala V, Christopher Octeau J, Kovoor A. Arrestin-dependent but G- protein coupled receptor kinase-independent uncoupling of D2-dopamine receptors. J Neurochem 2013;127:
7 Emery et al. 40 Kim KM, Valenzano KJ, Robinson SR, et al. Differential regulation of the dopamine D2 and D3 receptors by G protein-coupled receptor kinases and beta-arrestins. J Biol Chem 2001;276: Beaulieu JM, Gainetdinov RR, Caron MG. Akt/GSK3 signaling in the action of psychotropic drugs. Annu Rev Pharmacol Toxicol 2009;49: Beaulieu JM, Gainetdinov RR, Caron MG. The Akt-GSK-3 signaling cascade in the actions of dopamine. Trends Pharmacol Sci 2007;28: Takeuchi Y, Fukunaga K. Dopamine D2 receptor activates extracellular signal-regulated kinase through the specific region in the third cytoplasmic loop. J Neurochem 2004;89: Huang L, Wu DD, Zhang L, Feng LY. Modulation of A(2)a receptor antagonist on D(2) receptor internalization and ERK phosphorylation. Acta Pharmacol Sin 2013;34: Kim SJ, Kim MY, Lee EJ, Ahn YS, Baik JH. Distinct regulation of internalization and mitogen-activated protein kinase activation by two isoforms of the dopamine D2 receptor. Mol Endocrinol 2004;18: Choi EY, Jeong D, Park KW, Baik JH. G proteinmediated mitogen-activated protein kinase activation by two dopamine D2 receptors. Biochem Biophys Res Commun 1999;256: Quan W, Kim JH, Albert PR, Choi H, Kim KM. Roles of G protein and beta-arrestin in dopamine D2 receptor-mediated ERK activation. Biochem Biophys Res Commun 2008;377:
Bachelor of Arts Psychology, minor in Chemistry, Southern Illinois University Carbondale
Michael A. Emery Doctoral Candidate Interdisciplinary Program in Neuroscience Texas A&M Institute for Neuroscience (TAMIN) College Station, Texas 77843 emery87@tamu.edu ORCID: 0000 0002 8587 4115 Education
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 informationPotential for delta opioid receptor agonists as analgesics in chronic pain therapy
Potential for delta opioid receptor agonists as analgesics in chronic pain therapy David Kendall & Bengt von Mentzer; PharmNovo AB/UK Alex Conibear & Eamonn Kelly, University of Bristol Junaid Asghar,
More informationBehavioral Activation Induced by D 2 -Like Receptor Stimulation during Opiate Withdrawal 1
0022-3565/00/2942-0531$03.00/0 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 294, No. 2 Copyright 2000 by The American Society for Pharmacology and Experimental Therapeutics Printed in
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 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 informationPrevention of Development of Tolerance and Dependence to Opiate in Mice by BR-16A (Mentat) A Herbal Psychotropic Preparation
[Indian Journal of Experimental Biology (1992): (30), 885] Prevention of Development of Tolerance and Dependence to Opiate in Mice by BR-16A (Mentat) A Herbal Psychotropic Preparation Kulkarni, S.K. and
More informationBrain-Derived Neurotrophic Factor Levels in D2 Receptor Primed Adolescent Rats Given Twice Daily Nicotine Administrations.
East Tennessee State University Digital Commons @ East Tennessee State University Undergraduate Honors Theses 12-2011 Brain-Derived Neurotrophic Factor Levels in D2 Receptor Primed Adolescent Rats Given
More informationOpiate Use Disorder and Opiate Overdose
Opiate Use Disorder and Opiate Overdose Irene Ortiz, MD Medical Director Molina Healthcare of New Mexico and South Carolina Clinical Professor University of New Mexico School of Medicine Objectives DSM-5
More informationA BRIEF HISTORY OF G-PROTEIN COUPLED RECEPTORS
A BRIEF HISTORY OF G-PROTEIN COUPLED RECEPTORS Nobel Lecture Stockholm University December 8, 2012 Robert J. Lefkowitz, M.D. James B. Duke Professor of Medicine Investigator, Howard Hughes Medical Institute
More informationSUPPLEMENTARY INFORMATION
doi: 10.1038/nature06994 A phosphatase cascade by which rewarding stimuli control nucleosomal response A. Stipanovich*, E. Valjent*, M. Matamales*, A. Nishi, J.H. Ahn, M. Maroteaux, J. Bertran-Gonzalez,
More informationHow does polydrug use contribute to heroin overdose deaths? Risk to heroin users of concurrent use of pregabalin and gabapentin
How does polydrug use contribute to heroin overdose deaths? Risk to heroin users of concurrent use of pregabalin and gabapentin Graeme Henderson Suzanne Audrey Matt Hickman Abi Lyndon Rob Hill Claudia
More informationRecent Advances in Energy, Environment, Biology and Ecology
Acute and long-term effects elicited by psychoactive drugs on 50-kHz ultrasonic vocalizations in rats: development of a new experimental tool for the study of drug-mediated reward NICOLA SIMOLA Department
More informationSUPPLEMENTARY INFORMATION
Supplementary Figure 1. Behavioural effects of ketamine in non-stressed and stressed mice. Naive C57BL/6 adult male mice (n=10/group) were given a single dose of saline vehicle or ketamine (3.0 mg/kg,
More informationTHE OPIUM POPPY OPIOID PHARMACOLOGY 2/18/16. PCTH 300/305 Andrew Horne, PhD MEDC 309. Papaver somniferum. Poppy Seeds Opiates
OPIOID PHARMACOLOGY PCTH 300/305 Andrew Horne, PhD andrew.horne@ubc.ca MEDC 309 THE OPIUM POPPY Papaver somniferum Sleep-bringing poppy Poppy Seeds Opiates Opium Poppy Straw 1 OPIATES VS. OPIOIDS Opiates:
More informationNeuropharmacodynamic Profile of NKTR-181: Correlation to Low Abuse Potential
Neuropharmacodynamic Profile of NKTR-181: Correlation to Low Abuse Potential Laurie VanderVeen, Takahiro Miyazaki, Irene Choi, Michael A. Eldon, Xue Snow Ge, Hema Gursahani, Faye Hsieh, Aleksandrs Odinecs,
More informationFood restriction: enhancing effects on drug reward and striatal cell signaling
Food restriction: enhancing effects on drug reward and striatal cell signaling K.D. Carr Departments of Psychiatry & Pharmacology NYU School of Medicine Common Neural Substrates for Incentive-Motivating
More informationPAIN & ANALGESIA. often accompanied by clinical depression. fibromyalgia, chronic fatigue, etc. COX 1, COX 2, and COX 3 (a variant of COX 1)
Pain - subjective experience associated with detection of tissue damage ( nociception ) acute - serves as a warning chronic - nociception gone bad often accompanied by clinical depression fibromyalgia,
More informationSignalling profile differences: paliperidone versus risperidone
BJP British Journal of Pharmacology DOI:10.1111/bph.12295 www.brjpharmacol.org RESEARCH PAPER Signalling profile differences: paliperidone versus risperidone W P Clarke, T A Chavera, M Silva, L C Sullivan
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 informationLobeline Attenuates the Locomotor-Activating Properties of Repeated Morphine Treatment in Rats
Tropical Journal of Pharmaceutical Research August 2011; 10 (4): 421-429 Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved. Available online
More informationDifferential sensitivity to the acute and sensitizing behavioral effects of methylphenidate as a function of strain in adolescent and young adult rats
Yetnikoff and Arvanitogiannis Behavioral and Brain Functions 2013, 9:38 SHORT PAPER Open Access Differential sensitivity to the acute and sensitizing behavioral effects of methylphenidate as a function
More informationSHOSHANA EITAN, PH.D. ASSOCIATE PROFESSOR
SHOSHANA EITAN, PH.D. ASSOCIATE PROFESSOR Behavioral and Cellular Neuroscience Department of Psychological and Brain Sciences Texas A&M University College Station, TX 77843 Positions and Employment: 1997-2000
More informationOpioid Step Policy. Description. Section: Prescription Drugs Effective Date: April 1, 2018
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 Subject: Opioid Step Policy Page: 1 of 6 Last Review Date: March 16, 2018 Opioid Step Policy Description
More informationMark Edlund, MD, PhD RTI International. Photo courtesy of The Herb Museum, Vancouver, BC
Opioid Use Disorders and Their Treatment Mark Edlund, MD, PhD RTI International Photo courtesy of The Herb Museum, Vancouver, BC Acknowledgements Funded by NIDA R01 DA022560-01 NIDA R01 DA034627 NIDA R01
More informationAKT/GSK3 signaling cascade in dopamine actions
AKT/GSK3 signaling cascade in dopamine actions Jean-Martin Beaulieu, Raul R. Gainetdinov and Marc G. Caron Department of Cell Biology, Duke University Medical Center Durham, North Carolina 27710 Correspondence
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 informationOST. Pharmacology & Therapeutics. Leo O. Lanoie, MD, MPH, FCFP, CCSAM, ABAM, MRO
OST Pharmacology & Therapeutics Leo O. Lanoie, MD, MPH, FCFP, CCSAM, ABAM, MRO Disclaimer In the past two years I have received no payment for services from any agency other than government or academic.
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 informationFrom opium to analgesic tests: An introduction to the functioning and studying of the opioid system
Practice-oriented, student-friendly modernization of the biomedical education for strengthening the international competitiveness of the rural Hungarian universities TÁMOP-4.1.1.C-13/1/KONV-2014-0001 From
More informationThe Opiate Crisis 4/6/18. April 9, Words are important. If you want to care for something, you call it a flower.
The Opiate Crisis Presented by Dr. Anahi Ortiz Franklin County Coroner April 9, 2018 Words are important. If you want to care for something, you call it a flower. If you want to kill something, you call
More informationAlternatively spliced mu opioid receptor C termini impact the diverse actions of morphine
Alternatively spliced mu opioid receptor C termini impact the diverse actions of morphine Jin Xu,, Gavril W. Pasternak, Ying-Xian Pan J Clin Invest. 2017;127(4):1561-1573. https://doi.org/10.1172/jci88760.
More informationFunctional Selectivity at the -Opioid Receptor: Implications for Understanding Opioid Analgesia and Tolerance
0031-6997/11/6304-1001 1019$25.00 PHARMACOLOGICAL REVIEWS Vol. 63, No. 4 Copyright 2011 by The American Society for Pharmacology and Experimental Therapeutics 4598/3715875 Pharmacol Rev 63:1001 1019, 2011
More informationThinkTwice! Genetic Analysis Shows Gene Expression is Changed by Cocaine (Part II) JOURNAL ARTICLE TEI PLAIN LANGUAGE ANTHOLOGY C C
JOURNAL ARTILE Transformed into part of a plain language anthology Genetic Analysis Shows Gene Expression is hanged by ocaine (Part II) Abstract/Summary: hanges in gene activity are responsible for long-lasting
More information,, : Current Status in Drug Addiction and Addiction Memory Research WAN G Hao2Ran 1, GAO Xiang2 Rong 1, ZHAN G Kai2Gao 2, HAN Ji2Sheng 1 ( 1
202 2003 34 3 1 1 2 1 1 2 ( 100083) : R749. 91 Current Status in Drug Addiction and Addiction Memory Research WAN G Hao2Ran 1 GAO Xiang2 Rong 1 ZHAN G Kai2Gao 2 HAN Ji2Sheng 1 ( 1 D rug Dependence Peki
More informationPrescription Opioids
What are prescription opioids? Prescription Opioids Opioids are a class of drugs naturally found in the opium poppy plant. Some prescription opioids are made from the plant directly, and others are made
More informationAnalgesia for Patients with Substance Abuse Disorders. Lisa Jennings CN November 2015
Analgesia for Patients with Substance Abuse Disorders Lisa Jennings CN November 2015 Definitions n Addiction: A pattern of drug use characterised by aberrant drug-taking behaviours & the compulsive use
More informationBuprenorphine pharmacology
Buprenorphine pharmacology Victorian Opioid Management ECHO Department of Addiction Medicine St Vincent s Hospital Melbourne 2018 Page 1 Opioids full, partial, antagonist Full Agonists - bind completely
More informationA. Personal Statement
NAME: CHARTOFF, ELENA OMB No. 0925-0001 and 0925-0002 (Rev. 10/15 Approved Through 10/31/2018) BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors.
More informationOpioids- Indica-ons, Equivalence, Dependence and Withdrawal Methadone Maintenance (OST) Paul Glue
Opioids- Indica-ons, Equivalence, Dependence and Withdrawal Methadone Maintenance (OST) Paul Glue Scope Pharmacology of Opioids Equivalence Dependence and Withdrawal Methadone Maintenance (OST) 3 Opioid
More informationFentanyls and Naloxone. Opioids, Overdose, and Naloxone
Opioids, Overdose, and Naloxone Presenter Disclosure Presenter s Name: Michael Beazely I have no current or past relationships with commercial entities Speaking Fees for current program: I have received
More informationRhodiola rosea L- Standardized Extract on Passive
Research Article ISSN: 0976-5700 Rhodiola rosea L- Standardized Extract on Passive Avoidance in Rats Liliya Vl Vasileva 1,2,3*, Damyanka P Getova 3 1Department of Pharmacology and Clinical Pharmacology,
More informationAgonists at mu opioid receptors spin the wheels to keep the action going.
Molecular Pharmacology This article has Fast not been Forward. copyedited Published and formatted. on The October final version 20, may 2004 differ as from doi:10.1124/mol.104.008433 this version. Agonists
More informationEnhanced Rewarding Properties of Morphine, but not Cocaine, in arrestin-2 Knock-Out Mice
The Journal of Neuroscience, November 12, 2003 23(32):10265 10273 10265 Behavioral/Systems/Cognitive Enhanced Rewarding Properties of Morphine, but not Cocaine, in arrestin-2 Knock-Out Mice Laura M. Bohn,
More informationFrom opium to analgesic tests: An introduction to the functioning and studying of the opioid system
Practice-oriented, student-friendly modernization of the biomedical education for strengthening the international competitiveness of the rural Hungarian universities TÁMOP-4.1.1.C-13/1/KONV-2014-0001 From
More informationAdvancing Addiction Science to Address the Opioid Crisis
Advancing Addiction Science to Address the Opioid Crisis National Institute on Drug Abuse Bringing the full power of science to bear on drug abuse and addiction Nora D. Volkow, M.D. Director National Institute
More informationConstitutively Active Mu Opioid Receptors Mediate the Enhanced Conditioned Aversive Effect of Naloxone in Morphine-Dependent Mice
(2006) 31, 171 177 & 2006 Nature Publishing Group All rights reserved 0893-133X/06 $30.00 www.neuropsychopharmacology.org Constitutively Active Mu Opioid Receptors Mediate the Enhanced Conditioned Aversive
More informationHeroin What You Need to Know
Heroin What You Need to Know More People Died from Drug Overdoses than Car Crashes and Gun Deaths in 2015 52,404 people died from drug overdoses (33,091 involved an opioid including heroin) 37,757 people
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 informationOpiates & Opioids Opioids
Opiates & Opioids Opioids Opiates Pharmacologic principals important in primary care Present in opium from seedpod of Papaver somniferum Morphine, codeine Opioids Ted Parran MD FACP Are manufactured Isabel
More informationMedication Assisted Treatment of an Opioid Use Disorder. J. Craig Allen, MD. Medical Director, Rushford
Medication Assisted Treatment of an Opioid Use Disorder J. Craig Allen, MD. Medical Director, Rushford Learning objectives At the conclusion of this activity, participants will be able to: Understand
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 informationDOES THE D 3 DOPAMINE RECEPTOR (D 3 r)play A ROLE IN ADDICTION? Isabelle Boileau, PhD
DOES THE D 3 DOPAMINE RECEPTOR (D 3 r)play A ROLE IN ADDICTION? Isabelle Boileau, PhD Acknowledgments Human Neurochemical Pathology Lab Stephen J. Kish, PhD Jun Chao Tong, PhD Centre for Movement Disorders
More informationA Dopamine D2 Receptor-DISC1 Protein Complex may Contribute to Antipsychotic-Like Effects
Neuron Article A Dopamine D2 Receptor-DISC1 Protein Complex may Contribute to Antipsychotic-Like Effects Ping Su, 1,6 Shupeng Li, 1,6 Sheng Chen, 1 Tatiana V. Lipina, 2 Min Wang, 1 Terence K.Y. Lai, 1
More informationProtective Effect of Mentat (BR-16A) A Herbal Preparation, on Alcohol Abstinence-Induced Anxiety and Convulsions
[Indian Journal of Experimental Biology (1993): (31), 435] Protective Effect of Mentat (BR-16A) A Herbal Preparation, on Alcohol Abstinence-Induced Anxiety and Convulsions Kulkarni, S.K. and Anita Verma,
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 information6/6/2018. Nalbuphine: Analgesic with a Niche. Mellar P Davis MD FCCP FAAHPM. Summary of Advantages. Summary of Advantages
Nalbuphine: Analgesic with a Niche Mellar P Davis MD FCCP FAAHPM 1 Summary of Advantages Safe in renal failure- fecal excretion Analgesia equal to morphine with fewer side effects Reduced constipation
More informationUniversity of Colorado-Boulder
University of Colorado-Boulder Activated Glia as Culprits in Opposing Opioid Analgesia & Driving Tolerance, Dependence & Reward: Role of a Non-classical Non-classical Opioid Receptor Linda R. Watkins Psychology
More informationWhat do they have in common?
What do they have in common? Opioid use in USA Approximately 9 million people on long term opioids Approximated 5 million people reporting non-medical use of opioids 1997: 96mg/person morphine eq dispensed
More informationThe role of β-phenylethylamine in behavioral sensitization
The role of β-phenylethylamine in behavioral sensitization Hye Kyoung Park Department of Medical Science The Graduate School, Yonsei University The role of β-phenylethylamine in behavioral sensitization
More informationGrowth and Differentiation Phosphorylation Sampler Kit
Growth and Differentiation Phosphorylation Sampler Kit E 0 5 1 0 1 4 Kits Includes Cat. Quantity Application Reactivity Source Akt (Phospho-Ser473) E011054-1 50μg/50μl IHC, WB Human, Mouse, Rat Rabbit
More informationUltra-low-dose naltrexone suppresses rewarding effects of opiates and aversive effects of opiate withdrawal in rats
Psychopharmacology (2005) 181: 576 581 DOI 10.1007/s00213-005-0022-7 ORIGINAL INVESTIGATION Mary C. Olmstead. Lindsay H. Burns Ultra-low-dose naltrexone suppresses rewarding effects of opiates and aversive
More informationSarah A. Woller Texas A&M Institute for Neuroscience Department of Psychology College Station, TX
Education: B.S. Psychology University of Iowa May 2007 Sarah A. Woller Texas A&M Institute for Neuroscience Department of Psychology College Station, TX 77843 Email: sarah.woller@gmail.com M.S. Psychology
More informationModulation of Oral Morphine Antinociceptive Tolerance and Naloxone-Precipitated Withdrawal Signs by Oral
0022-3565/03/3053-812 817$7.00 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 305, No. 3 Copyright 2003 by The American Society for Pharmacology and Experimental Therapeutics 46870/1059085
More informationD. Nishizawa 1, N. Gajya 2 and K. Ikeda 1, * Global Research & Development, Nagoya Laboratories, Pfizer Japan Inc, Nagoya, Japan
Current Neuropharmacology, 2011, 9, 113-117 113 Identification of Selective Agonists and Antagonists to G Protein-Activated Inwardly Rectifying Potassium Channels: Candidate Medicines for Drug Dependence
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 informationChronic Morphine Treatment Reduces Recovery from Opioid Desensitization
The Journal of Neuroscience, September 1, 2004 24(35):7699 7706 7699 Behavioral/Systems/Cognitive Chronic Morphine Treatment Reduces Recovery from Opioid Desensitization Vu C. Dang and John T. Williams
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 informationLONG TERM PHARMACOTHERAPY OF OPIOID DEPENDENCE
LONG TERM PHARMACOTHERAPY OF OPIOID DEPENDENCE DR. SHILPA ADARKAR ASSOCIATE PROFESSOR DEPARTMENT OF PSYCHIATRY & DRUG DEADDICTION CENTRE OF EXCELLENCE SETH GSMC & KEMH LONG TERM OPTIONS FULL AGONIST PARTIAL
More informationTRAMADOL, A CENTRALLY ACTING OPIOID : ANTICONVULSANT EFFECT AGAINST MAXIMAL ELECTROSHOCK SEIZURE IN MICE
Indian J Physiol Pharmacol 1998; 42 (3) : 407-411 TRAMADOL, A CENTRALLY ACTING OPIOID : ANTICONVULSANT EFFECT AGAINST MAXIMAL ELECTROSHOCK SEIZURE IN MICE ANSHU MANOCHA, KRISHNA K. SHARMA* AND PRAMOD K.
More informationOpiates: Good or Bad? Mandeep Pabla, Julie Lee, Kelsey Lee
Opiates: Good or Bad? Mandeep Pabla, Julie Lee, Kelsey Lee A young woman pregnant with her first child makes a visit to her obstetrician. She imagines holding her baby as she sees the black and white sonogram.
More informationSpotlight on Health Policy Beyond the Clinical: The Opioid Epidemic. October 25, 2017
Spotlight on Health Policy Beyond the Clinical: The Opioid Epidemic October 25, 2017 Disclosures and Disclaimer Neither the Institute for Health Policy and Leadership (IHPL) nor I have any relevant financial
More informationQualifying Examination (Part I)
Department of Pharmacology Qualifying Examination (Part I) December 12 & 13, 2006 Please remember that this is a closed-book examination. You must be prepared to answer 4 of the 7 questions. Although not
More informationEffects of a Novel Fentanyl Derivative on Drug Discrimination and Learning in Rhesus Monkeys
PII S0091-3057(99)00058-1 Pharmacology Biochemistry and Behavior, Vol. 64, No. 2, pp. 367 371, 1999 1999 Elsevier Science Inc. Printed in the USA. All rights reserved 0091-3057/99/$ see front matter Effects
More informationNew Approaches in the Development of Opioids and Other Analgesics. Thomas E. Prisinzano, PhD Department of Medicinal Chemistry School of Pharmacy
New Approaches in the Development of pioids and ther Analgesics Thomas E. Prisinzano, PhD Department of Medicinal Chemistry School of Pharmacy Disclosures The University of Iowa Research Foundation has
More informationOverview of Opioid Use Disorder
Overview of Opioid Use Disorder Doug Burgess, MD Medical Director of Outpatient Services, Truman Medical Centers Assistant Professor of Psychiatry, University of Missouri- Kansas City Objectives History
More informationAnalgesics, pain and tolerance: The St John s discussion
EDITORIAL Analgesics, pain and tolerance: The St John s discussion Four of the articles in the present issue of Pain Research & Management discuss preclinical issues relevant to understanding the changes
More informationOpioid Epidemic as it Relates to Counties
89 TH ANNUAL WEST TEXAS COUNTY JUDGES AND COMMISSIONERS ASSOCIATION CONFERENCE Wednesday, April 25, 2018 11:05 11:55 a.m. Opioid Epidemic as it Relates to Counties Ms. Jessica Cance Agency Analytics Unit
More informationNoel Schenk MD. Davis Behavioral Health
Noel Schenk MD Davis Behavioral Health Michael Botticelli Director of National Drug Control Policy What is Addiction? Addiction is defined as a chronic, relapsing brain disease that is characterized by
More informationNitric oxide (NO) and central dopamine (DA) D3 receptor reactivity to quinpirole in rats
Nitric oxide (NO) and central dopamine (DA) D3 receptor reactivity to quinpirole in rats Ryszard ~rusl, Ryszard szkilnik1 and Richard M. ~ostrzewa~ '~e~artment of Pharmacology, Silesian Academy of Medicine,
More informationOpiate Use among Ohio Medicaid Recipients
Opiate Use among Ohio Medicaid Recipients July 12, 2012 Ohio Colleges of Medicine Government Resource Center The Ohio State University College of Public Health Sponsored by The Ohio Department of Alcohol
More informationOpioid Overdose Best Practices Guideline. Table of Contents. A. General description: B: Typical signs and symptoms:
Opioid Overdose Best Practices Guideline Table of Contents A. General description B. Typical signs and symptoms C. Expected course D. Making the diagnosis E. Recommended treatment F. Criteria for hospital
More informationAnalgesia is a labeled indication for all of the approved drugs I will be discussing.
Comparative Opioid Pharmacology Disclosure Analgesia is a labeled indication for all of the approved drugs I will be discussing. I ve consulted with Glaxo (remifentanil), Abbott (remifentanil), Janssen
More informationMorphine analgesic tolerance in 129P3/J and 129S6/SvEv mice
Pharmacology, Biochemistry and Behavior 85 (2006) 769 779 www.elsevier.com/locate/pharmbiochembeh Morphine analgesic tolerance in 129P3/J and 129S6/SvEv mice Camron D. Bryant a,b,c,, Kristofer W. Roberts
More informationP arkinson s disease (PD) is a neurodegenerative disorder characterized by the loss of nigrostriatal dopaminergic
SUBJECT AREAS: BEHAVIOUR RECEPTORS MODELLING PATHOLOGY The role of GRK6 in animal models of Parkinson s Disease and L-DOPA treatment Francesca Managò 1, Stefano Espinoza 1, Ali Salahpour 2, Tatyana D.
More information3/15/2018. Pain. Pain. Opioid Analgesics Addiction. Pain
Pain Pain Well, I guess that explains the abdominal pains. Well, I guess that explains the abdominal pains. Pain is a component of virtually all clinical strategies, and management of pain is a primary
More informationBitter Taste Receptors: Taking a Bigger Bite of Airway Smooth Muscle Pathophysiology
Page 1 of 6 Editorial Bitter Taste Receptors: Taking a Bigger Bite of Airway Smooth Muscle Pathophysiology Charles W. Emala, Sr. Department of Anesthesiology Columbia University, New York, New York Contact
More informationSupplementary Figure 1. Western blot of hippocampal lysates from WT and Adcy1 KO mice demonstrates the specificity of the ADCY1 antibody.
ADCY1 13 kda β-actin 45 kda Supplementary Figure 1. Western blot of hippocampal lysates from and mice demonstrates the specificity of the ADCY1 antibody. a DHPG perk1/2 ERK1/2 Relative level min 1.6 *
More informationMorphine Side Effects in -Arrestin 2 Knockout Mice
0022-3565/05/3143-1195 1201$20.00 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 314, No. 3 Copyright 2005 by The American Society for Pharmacology and Experimental Therapeutics 87254/3045361
More informationNational Academies of Sciences, Engineering, and Medicine Forum on Neuroscience and Nervous System Disorders
National Academies of Sciences, Engineering, and Medicine Forum on Neuroscience and Nervous System Disorders Workshop: Advancing Therapeutic Development for Pain and Opioid Use Disorders through Public-Private
More informationOHIO S OPIOID DRUG OVERDOSE EPIDEMIC: CONTRIBUTING FACTORS AND ONGOING PREVENTION EFFORTS
OHIO S OPIOID DRUG OVERDOSE EPIDEMIC: CONTRIBUTING FACTORS AND ONGOING PREVENTION EFFORTS DEFINITIONS Opiate- originate from naturally-occurring elements found in the opium poppy plant. These drugs are
More informationDopamine in Ube3a m-/p+ mice. Online Supplemental Material
Online Supplemental Material S1 Supplemental Figure 1. Schematic of rate-dependent intracranial self-stimulation (ICSS) (A) Mice implanted with monopolar stimulating electrodes to the medial forebrain
More informationThe effects of environmental enrichment on nicotine sensitization in a rodent model of schizophrenia
East Tennessee State University Digital Commons @ East Tennessee State University Undergraduate Honors Theses 5-2014 The effects of environmental enrichment on nicotine sensitization in a rodent model
More informationAddiction Overview. Diane A. Rothon MD. Causes Consequences Treatments. Methadone/Buprenorphine 101 April 1, 2017
Addiction Overview Causes Consequences Treatments Methadone/Buprenorphine 101 April 1, 2017 Diane A. Rothon MD Why? would you listen to this presentation Review the definition and neurobiology of addiction
More informationHHS Priorities and Actions to Support Treatment for Those with Opioid Use Disorder
HHS Priorities and Actions to Support Treatment for Those with Opioid Use Disorder Brett Giroir, U.S. Department of Health and Human Services Join the conversation at #OUDTreatment #EndTheStigma Expanding
More informationThe Unseen Consequences of Prescription Drug Abuse. Stephen Loyd, M.D.
The Unseen Consequences of Prescription Drug Abuse Stephen Loyd, M.D. Stephen Loyd, M.D. Receives no commercial support, in any form, from pharmaceutical companies or anyone else Medical Director for Substance
More informationMedications in the Treatment of Opioid Use Disorder: Methadone and Buprenorphine What Really Are They?
Medications in the Treatment of Opioid Use Disorder: Methadone and Buprenorphine What Really Are They? Yngvild Olsen, MD, MPH Cecil County Board of Health Workgroup Meeting Elkton, MD October 8, 2013 Objectives
More informationNeuroprotection in preclinical models of Parkinson disease by the NAPVSIPQ peptide
Neuroprotection in preclinical models of Parkinson disease by the NAPVSIPQ peptide Bruce H. Morimoto, Ph.D. Executive Director, Applied Translational Medicine Microtubules Microtubules essential for neuronal
More informationOpioids. Sergio Hernandez, MD
Opioids Sergio Hernandez, MD Required Slide Disclosures 1. SIGNIFICANT FINANCIAL INTERESTS NO SIGNIFICANT FINANCIAL, GENERAL, OR OBLIGATION INTERESTS TO REPORT 2. GENERAL AND OBLIGATION INTERESTS All general
More informationArticle #2 Prescription Drug Overdose CDC: Centers for Disease Control and Prevention. Understanding the Epidemic
Article #2 Prescription Drug Overdose CDC: Centers for Disease Control and Prevention Understanding the Epidemic When the Prescription Becomes the Problem In a period of nine months, a tiny Kentucky county
More information