Effects of drugs that potentiate GABA on extinction of positively-reinforced operant behaviour.
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.
Leslie
Julian C
JC
School of Psychology, University of Ulster, Shore Road, Newtownabbey BT37 0QB, UK. jc.leslie@ulster.ac.uk
Shaw
David
D
McCabe
Ciara
C
Reynolds
David S
DS
Dawson
Gerard R
GR
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D004357:Drug Synergism; D005108:Extinction, Psychological / Q000187:drug effects* / Q000502:physiology; D005639:Frustration; D018755:GABA Agonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D012054:Reinforcement, Psychology; D000077334:Zolpidem; D005680:gamma-Aminobutyric Acid / Q000187:drug effects* / Q000502:physiology
D014151:Anti-Anxiety Agents; D018755:GABA Agonists; D011725:Pyridines; D005680:gamma-Aminobutyric Acid; D000077334:Zolpidem