Facilitation of extinction and re-extinction of operant behavior in mice by chlordiazepoxide and D-cycloserine

The aim was to compare operant extinction with re-extinction following re-acquisition and to investigate neuropharmacological mechanisms through administration of drugs potentiating GABAergic or glutamatergic systems. Groups of C57Bl/6 mice were trained to lever press for food on a fixed ratio schedule, then extinguished with or without pre-session chlordiazepoxide or post-session D-cycloserine administration (15 mg/kg in each case), then retrained to lever press for food, then re-extinguished with or without pre-session chlordiazepoxide or post-session D-cycloserine. Under vehicle injections, extinction and re-extinction curves were indistinguishable, but drug treatments showed that there was less resistance to extinction in the re-extinction phase. Chlordiazepoxide facilitated extinction and re-extinction, with an earlier effect during re-extinction. D-Cycloserine also facilitated extinction and re-extinction, with some evidence of an earlier effect during re-extinction. These results replicate and extend earlier findings with operant extinction, but differ from some previous reports of D-cycloserine on re-extinction of Pavlovian conditioned fear. Implications for accounts of the similarities and differences between neural mechanisms of extinction following either Pavlovian or operant conditioning, and applications of these findings, are discussed. (C) 2013 Elsevier Inc. All rights reserved.