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Subtype-selective GABAergic drugs facilitate extinction of mouse operant behaviour

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

McCabe, C, Shaw, David, Atack, JR, Street, LJ, Wafford, KA, Dawson, GR, Reynolds, DS and Leslie, Julian (2004) Subtype-selective GABAergic drugs facilitate extinction of mouse operant behaviour. NEUROPHARMACOLOGY, 46 (2). pp. 171-178. [Journal article]

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DOI: 10.1016/j.neuropharm.2003.09.004

Abstract

Several recent studies have shown that reducing gamma-aminobutyric acid (GABA)-mediated neurotransmission retards extinction of aversive conditioning. However, relatively little is known about the effect of GABA on extinction of appetitively motivated tasks. We examined the effect of chlordiazepoxide (CDP), a classical benzodiazepine (BZ) and two novel subtype-selective BZs when administered to male C57B1/6 mice during extinction following training on a discrete-trial fixed-ratio 5 (FR5) food reinforced lever-press procedure. Initially CDP had no effect, but after several extinction sessions CDP significantly facilitated extinction, i.e. slowed responding, compared with vehicle-treated mice. This effect was not due to drug accumulation because mice switched from vehicle treatment to CDP late in extinction showed facilitation immediately. Likewise, this effect could not be attributed to sedation because the dose of CDP used (15 mg/kg i.p.) did not suppress locomotor activity. The two novel subtype-selective BZ partial agonists, L838,417 and TP13, selectively facilitated extinction in similar fashion to CDP. The non-GABAergic anxiolytic buspirone was also tested and found to have similar effects when administered at a non-sedating dose. These studies demonstrate that GABA-mediated processes are important during extinction of an appetitively motivated task, but only after the animals have experienced several extinction sessions. (C) 2003 Elsevier Ltd. All rights reserved.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Psychology
Research Institutes and Groups:Psychology Research Institute
Psychology Research Institute > Behavioural Neuroscience & Behavioural Analysis
ID Code:1653
Deposited By:Mrs Fiona Harkin
Deposited On:23 Dec 2009 09:32
Last Modified:13 Mar 2012 16:33

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