Psychopharmacology

, Volume 202, Issue 1, pp 397–402

Facilitation of extinction of operant behaviour in mice by d-cycloserine

  • David Shaw
  • Kelly Norwood
  • Kim Sharp
  • Lauren Quigley
  • Stephen F. J. McGovern
  • Julian C. Leslie
Original Investigation

DOI: 10.1007/s00213-008-1312-7

Cite this article as:
Shaw, D., Norwood, K., Sharp, K. et al. Psychopharmacology (2009) 202: 397. doi:10.1007/s00213-008-1312-7

Abstract

Rationale and objective

The N-methyl-d-aspartate receptor agonist d-cycloserine (DCS) facilitates extinction following Pavlovian fear conditioning or conditioned place preference in rats, but its effects on extinction following operant conditioning are not previously established. We studied the effects of DCS on operant extinction with mice, previously shown to be facilitated by GABAergic potentiators including chlordiazepoxide.

Materials and methods

Following training of lever pressing by C57Bl/6 male mice on a discrete-trial fixed-ratio food reinforcement schedule with six reinforcers per session, 48-trial extinction sessions were conducted at 3- (Experiment 1) or 4-day intervals (Experiment 2). Effects of DCS (15 or 30 mg/kg, i.p.) administered immediately after 48-trial extinction sessions were compared with those of saline injections.

Results

With 3-day intervals between extinction sessions, post-session administration of DCS facilitated extinction, and this effect was stronger with 4-day intervals between extinction sessions. Facilitation of extinction by post-session drug administration persisted over a number of extinction sessions.

Conclusions

Operant extinction in mice can be facilitated by DCS, a glutamatergic agonist, as well as by GABAergic potentiators. The relationship between glutamatergic and GABAergic processes in operant extinction is yet to be established. These findings strengthen the basis for clinical uses of DCS.

Keywords

Operant conditioning Extinction d-Cycloserine C57Bl/6 mice 

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • David Shaw
    • 1
  • Kelly Norwood
    • 1
  • Kim Sharp
    • 1
  • Lauren Quigley
    • 1
  • Stephen F. J. McGovern
    • 1
  • Julian C. Leslie
    • 1
  1. 1.School of PsychologyUniversity of UlsterColeraineUK

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