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

Abstract

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.

Animal Models of Psychiatric Disorders: Behaviour Analysis Perspectives

“…We used two doses of CDP as we wanted to check the dose response relationship with this new procedure. In parallel with our previous published reports (e.g., Leslie et al, 2004;Shaw et al, 2009), times taken to complete the five-response sequence of presses on the two levers were log transJulian C. Leslie formed to improve homogeneity of variance, and then group data were submitted to mixed analyses of variance with blocks of trials in extinction sessions as a within-subject factor, and drug treatment as a between-subjects factor (genotype was also a between-subjects factor in some of the experiments reported below). The effects reported below were all significant as main effects and supported by significant pair-wise post-hoc comparisons between groups (p<0.05 in all cases).…”

“…This partial agonist of the glutamatergic NMDA receptor facilitates extinction of classically conditioned fear, and this has led to it being used clinically in the treatment of post-traumatic stress disorder. Using C57Bl/6 mice, we found that facilitation occurred when DCS was administered after (but not before) extinction sessions (Shaw, Norwood, Sharp, Quigley, McGovern, & Leslie, 2009), replicating findings with extinction of conditioned fear responses (Ledgerwood, Richardson, & Cranney, 2003) and appetitive conditioned place preference (Botreau, Paolone, Stewart, 2006) in rats. There is a consensus in the behavioural neuroscience literature that extinction involves "new learning"; that inhibition of the previously learnt behaviour develops during extinction, and this is mediated by different brain systems than those involved in the original learning of the conditioned behaviour.…”

“…The response required at each point was not signaled but in the experiments to be reported here the requirement was RLLRL. As before (e.g., Shaw et al, 2009), C57Bl/6 mice were trained until an asymptotic performance developed on this task. Although 6-trial sessions were used in training to avoid satiation with food, 48-trial sessions were used in extinction when that consideration does not apply.…”

Behavioral neuroscience of psychological pain

“…However, there was a difference between these two d-cycloserine studies. Whereas dcycloserine had an effect in the early portion of a consummatory session in the cSNC situation (Norris et al, 2011), d-cycloserine did not disrupt spontaneous recovery of responding during the early portion of the subsequent session in appetitive extinction (Shaw et al, 2009).…”

“…Just as d-cycloserine enhanced the cSNC effect, it also accelerated appetitive extinction. In one experiment, Shaw et al (2009) trained mice in a fixed-ratio 5 schedule before downshifting them to extinction. d-cycloserine administered immediately after each extinction session facilitated extinction performance.…”