Facilitation of extinction of operant behaviour in C57Bl/6 mice by chlordiazepoxide and d-cycloserine

• Published in: Psychopharmacology 2012-09, Vol.223 (2), p.223-235
• Main Authors: Leslie, Julian C., Norwood, Kelly, Kennedy, Paul J., Begley, Michael, Shaw, David
• Format: Article
• Language: English
• Subjects: Animal behavior; Animal experimentation; Animal memory; Animals; Behavior, Animal - drug effects; Biomedical and Life Sciences; Biomedicine; chlordiazepoxide; Chlordiazepoxide - administration & dosage; Chlordiazepoxide - pharmacology; Conditioning, Operant - drug effects; Cycloserine; Cycloserine - administration & dosage; Cycloserine - pharmacology; Discrimination Learning - drug effects; Drugs; Extinction; Extinction, Psychological - drug effects; Flumazenil; Food; GABA; gamma -Aminobutyric acid; Glutamatergic transmission; Learning; Male; Mice; Mice, Inbred C57BL; Neurosciences; Neurotransmitters; Operant conditioning; Original Investigation; Palatability; Pharmacology/Toxicology; Psychiatry; Psychopharmacology; Psychotropic drugs; Reinforcement Schedule; Rodents; Withdrawal
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-012-2710-4

Rationale and objective Effects on the extinction of GABAergic drug, chlordiazepoxide (CDP), and glutamatergic drug, d -cycloserine (DCS), in C57BL/6 mice were compared. Materials and methods Following a palatability test ( Experiment 1 ), Experiments 2 – 6 involved food-reinforced lever press training followed by extinction sessions at 1- or 4-day intervals. The effects of drugs were examined. Experiment 7 involved a two-lever task. Results CDP did not affect food palatability ( Experiment 1 ), but facilitated extinction when administered prior to extinction sessions via intracerebral ( Experiment 2 ) or peripheral administration at 1-day ( Experiments 3 – 7 ) or 4-day intervals ( Experiment 6 ). Reducing the amount of training prior to extinction reduced the delay in the effect of CDP typically seen, and CDP had a larger effect in early sessions on mice that had received less training ( Experiment 3 ). There was some evidence that CDP could be blocked by flumazenil ( Experiment 4 ), and CDP withdrawal reversed extinction facilitation ( Experiments 5 and 7 ). With 4-day intervals, DCS administered immediately following extinction sessions, or pre-session CDP, facilitated extinction with 48-trial sessions (experiment 6B). With six-trial sessions, the co-administration of post-session DCS enhanced facilitation produced by pre-session CDP (experiment 6A). Finally, CDP facilitated extinction in a dose-related fashion following training on a two-lever food-reinforced task ( Experiment 7 ). Conclusions The findings are consistent with the hypotheses that two neurotransmitter systems have different roles in operant extinction and that glutamatergic systems are involved in extinction learning and GABAergic systems involved in the expression of that learning. This parallels findings with extinction following Pavlovian conditioning, which has been more extensively investigated.