Subtype-selective GABAergic drugs facilitate extinction of mouse operant behaviour

C McCabe, David Shaw, JR Atack, LJ Street, KA Wafford, GR Dawson, DS Reynolds, Julian Leslie

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.
LanguageEnglish
Pages171-178
JournalNeuropharmacology
Volume46
Issue number2
DOIs
Publication statusPublished - Feb 2004

Fingerprint

Chlordiazepoxide
Pharmaceutical Preparations
gamma-Aminobutyric Acid
Benzodiazepines
Buspirone
Psychological Extinction
Anti-Anxiety Agents
Locomotion
Synaptic Transmission
Food

Cite this

McCabe, C ; Shaw, David ; Atack, JR ; Street, LJ ; Wafford, KA ; Dawson, GR ; Reynolds, DS ; Leslie, Julian. / Subtype-selective GABAergic drugs facilitate extinction of mouse operant behaviour. In: Neuropharmacology. 2004 ; Vol. 46, No. 2. pp. 171-178.
@article{797e1cffc58645b5ac86ebf34409eb7d,
title = "Subtype-selective GABAergic drugs facilitate extinction of mouse operant behaviour",
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.",
author = "C McCabe and David Shaw and JR Atack and LJ Street and KA Wafford and GR Dawson and DS Reynolds and Julian Leslie",
year = "2004",
month = "2",
doi = "10.1016/j.neuropharm.2003.09.004",
language = "English",
volume = "46",
pages = "171--178",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier",
number = "2",

}

McCabe, C, Shaw, D, Atack, JR, Street, LJ, Wafford, KA, Dawson, GR, Reynolds, DS & Leslie, J 2004, 'Subtype-selective GABAergic drugs facilitate extinction of mouse operant behaviour', Neuropharmacology, vol. 46, no. 2, pp. 171-178. https://doi.org/10.1016/j.neuropharm.2003.09.004

Subtype-selective GABAergic drugs facilitate extinction of mouse operant behaviour. / McCabe, C; Shaw, David; Atack, JR; Street, LJ; Wafford, KA; Dawson, GR; Reynolds, DS; Leslie, Julian.

In: Neuropharmacology, Vol. 46, No. 2, 02.2004, p. 171-178.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Subtype-selective GABAergic drugs facilitate extinction of mouse operant behaviour

AU - McCabe, C

AU - Shaw, David

AU - Atack, JR

AU - Street, LJ

AU - Wafford, KA

AU - Dawson, GR

AU - Reynolds, DS

AU - Leslie, Julian

PY - 2004/2

Y1 - 2004/2

N2 - 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.

AB - 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.

U2 - 10.1016/j.neuropharm.2003.09.004

DO - 10.1016/j.neuropharm.2003.09.004

M3 - Article

VL - 46

SP - 171

EP - 178

JO - Neuropharmacology

T2 - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 2

ER -