Facilitation of extinction of operant behaviour in mice by D-cycloserine.
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.


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.
Shaw
David
D
School of Psychology, University of Ulster, Coleraine BT521SA, Northern Ireland, UK.
Norwood
Kelly
K
Sharp
Kim
K
Quigley
Lauren
L
McGovern
Stephen F J
SF
Leslie
Julian C
JC
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D003523:Cycloserine / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects*; D005502:Food; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018697:Nootropic Agents / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology
D018697:Nootropic Agents; D016194:Receptors, N-Methyl-D-Aspartate; D003523:Cycloserine
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