Hannah Dinnen and Ivy Farr THE EFFECTS OF BENZODIAZEPINES ON FEEDING BEHAVIOR
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1 Hannah Dinnen and Ivy Farr THE EFFECTS OF BENZODIAZEPINES ON FEEDING BEHAVIOR
2 Benzodiazepines GABA agonists increase effect of GABA, a general inhibitory NT Anti-anxiety drugs (7.3% U.S. population) Prescription versions: Valium, Xanax Chlordiazepoxide (CDP) Librium Side effect is weight gain
3 How do benzodiazepines lead to weight gain? Benzodiazepines stimulate feeding behavior Caused by removal of anxiety (motivation)? Caused by a change in palatability? Sucrose and other palatable stimuli Increases consumption selectively Few studies of aversive stimuli
4 Our Experiment Question: Does CDP increase palatability of appetitive and/or aversive stimuli? Effects on palatability measured by changes in licking responses Tastants from 4 taste categories: appetitive (sucrose) aversive (sodium chloride, citric acid, quinine) Male and female Sprague-Dawley rats
5 Long Term Protocol Licking measured over 9 min in AC 18 lickometer 75 mm Sucrose, 5 mm NaCl, 3 mm Citric Acid,.5 mm Quinine Influenced by palatability and post-ingestive feedback mechanisms Microstructural analysis of licking behavior First minute licks (palatability) Total number of licks (satiety/palatability) Meal duration (satiety) & Meal Licks (palatability) Pause Duration & Licking Rate (palatability) Hypothesis: If benzodiazepines selectively increase palatability, then microstructural analysis measures related to taste cues should increase under the influence of CDP as compared to saline with little or no change to measures related to satiety
6 Long Term Results First Minute Licks Licks Water
7 Long Term Results First Minute Licks 4 35 # Saline CDP 3 25 Licks Water NaCl Sucrose Citric Acid Quinine
8 Long Term Results Session Licks 5 45 Saline CDP 4 35 Licks NaCl Sucrose Citric Acid Quinine
9 Long Term Results Meals (Groups of Licks; Pause >1min ends meal) Changes in Meal Duration associated with hunger / satiety MEAL DURATION Saline CDP Second NaCl Sucrose Citric Acid Quinine
10 Long Term Results Meals (Groups of Licks; Pause >1min ends meal) MEAL LICKS 45 4 Saline CDP 35 3 Licks Changes in Meal Duration associated with hunger / satiety NaCl Sucrose Citric Acid Quinine Changes in Meal Licks associated with palatability MEAL DURATION Saline CDP 12 Seconds NaCl Sucrose Citric Acid Quinine
11 Long Term Results Pauses within Meals Saline CDP Seconds NaCl Sucrose Citric Acid Quinine
12 Long Term Results Lick Rate Saline CDP Licks / s NaCl Sucrose Citric Acid Quinine
13 Short-Term Testing CDP or Saline, i.p. injections 15s stimulus trials 4 Tastants: Sweet: Sucrose (25, 5, 1, 5 mm) Salty: NaCl (125, 25, 5, 1 mm) Sour: Citric Acid (7, 15, 3, 6 mm) Bitter: QHCl (.3,.13,.5,.2 mm) Hypothesis: If benzodiazepines increase palatability, then licking should increase under the influence of CDP as compared to saline
14 The Davis Rig Phase 1: Short-term Testing
15 Short Term Results Sucrose # F-CDP F-Saline M-CDP M-Saline Licks / 15s Sucrose (mm)
16 Short Term Results # Sucrose F-CDP F-Saline M-CDP M-Saline Licks / 15s Sucrose (mm)
17 Short Term Results Salty, Males Only 1.2 Saline 1 Lick Ratio NaCl (mm)
18 Short Term Results Salty, Males Only 1.2 CDP Saline 1 Lick Ratio NaCl (mm)
19 Short Term Results Sour 1.2 CDP Saline 1.8 Lick Ratio Citric Acid (mm)
20 Short Term Results Bitter CDP Saline Lick Ratio Quinine (mm)
21 Results Summary Microanalysis of long-term testing showed effects for measures associated with palatability First-minute licks, meal licks, pause duration, licking rate Short-term testing confirmed increases in palatability for both appetitive and aversive stimuli Sucrose: ceiling effect, but CDP increased licking at lower concentrations NaCl: more palatable after CDP for males CA and Quinine: more palatable after CDP
22 Conclusions Increase in palatability with benzodiazepines This research expands on previous reports: Both short term and long term testing Analysis of licking behavior not just stimulus consumption Both appetitive and aversive stimuli Important Implications Taste system neurophysiology: GABA regulation of taste Clinical relevance: Benzo side effects Potential Applications: Treatment for eating disorders related to changes in palatability
23 Special thanks to: Dr. Baird (Amherst College) for his help in analyzing the long term data Tyler Toomes for his help with data collection Dr. Pittman for his continuing guidance and support throughout this study
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