Effects of drugs that potentiate GABA on extinction of positively-reinforced operant behaviour

Julian Leslie, David Shaw, C McCabe, DS Reynolds, GR Dawson

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Extinction following positively reinforced operant conditioning reduces response frequency, at least in part through the aversive or frustrative effects of non-reinforcement. According to J.A. Gray's theory, non-reinforcement activates the behavioural inhibition system which in turn causes anxiety. As predicted, anxiolytic drugs including benzodiazepines affect the operant extinction process. Recent studies have shown that reducing GABA-mediated neurotransmission retards extinction of aversive conditioning. We have shown in a series of studies that anxiolytic compounds that potentiate GABA facilitate extinction of positively reinforced fixed-ratio operant behaviour in C57B1/6 male mice. This effect does not occur in the early stages of extinction, nor is it dependent on cumulative effects of the compound administered. Potentiation of GABA at later stages has the effect of increasing sensitivity to the extinction contingency and facilitates the inhibition of the behaviour that is no longer required. The GABAergic hypnotic, zolpidem, has the same selective effects on operant extinction in this procedure. The effects of zolpidem are not due to sedative action. There is evidence across our series of experiments that different GABA-A subtype receptors are involved in extinction facilitation and anxiolysis. Consequently, this procedure may not be an appropriate model for anxiolytic drug action, but it may be a useful technique for analysing the neural bases of extinction and designing therapeutic interventions in humans where failure to extinguish inappropriate behaviours can lead to pathological conditions such as post-traumatic stress disorder. (C) 2004 Elsevier Ltd. All rights reserved.
LanguageEnglish
Pages229-238
JournalNeuroscience and Biobehavioral Reviews
Volume28
Issue number3
DOIs
Publication statusPublished - May 2004

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gamma-Aminobutyric Acid
Pharmaceutical Preparations
Anti-Anxiety Agents
Hypnotics and Sedatives
Operant Conditioning
Psychological Extinction
GABA-A Receptors
Post-Traumatic Stress Disorders
Benzodiazepines
Synaptic Transmission
Anxiety

Cite this

Leslie, Julian ; Shaw, David ; McCabe, C ; Reynolds, DS ; Dawson, GR. / Effects of drugs that potentiate GABA on extinction of positively-reinforced operant behaviour. In: Neuroscience and Biobehavioral Reviews. 2004 ; Vol. 28, No. 3. pp. 229-238.
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Effects of drugs that potentiate GABA on extinction of positively-reinforced operant behaviour. / Leslie, Julian; Shaw, David; McCabe, C; Reynolds, DS; Dawson, GR.

In: Neuroscience and Biobehavioral Reviews, Vol. 28, No. 3, 05.2004, p. 229-238.

Research output: Contribution to journalArticle

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