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.
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Acknowledgements
This research was supported by a grant from the U.K. Biotechnology and Biological Sciences Research Council. Experimental procedures were in accordance with the UK Animals (Scientific Procedures) Act (1986) and its associated guidelines. We are indebted to Michael Begley and Paul Kennedy for assistance in running Experiment 2.
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Shaw, D., Norwood, K., Sharp, K. et al. Facilitation of extinction of operant behaviour in mice by d-cycloserine. Psychopharmacology 202, 397–402 (2009). https://doi.org/10.1007/s00213-008-1312-7
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DOI: https://doi.org/10.1007/s00213-008-1312-7