Chronic elevation of brain GABA by gamma-vinyl GABA treatment does not alter the sensitivity of GABAergic or dopaminergic receptors in rat CNS

Rat brain GABA levels were elevated chronically by daily administration of gamma-vinyl GABA, an enzyme-activated, irreversible inhibitor of GABA:2-oxo-glutarate aminotransferase (GABA-T; EC2.6.1.19). Following various periods of drug treatment and withdrawal, the sensitivity of dopamine and GABA rec...

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Bibliographic Details
Published in:Psychopharmacology 1983-01, Vol.79 (2-3), p.130-136
Main Authors: Gardner, C R, Mallorga, P, Klein, J, Huot-Olivier, S, Palfreyman, M G
Format: Article
Language:English
Subjects:
Adenylyl Cyclases - metabolism
Aminocaproates - pharmacology
Animals
Brain Chemistry - drug effects
Diazepam - metabolism
gamma-Aminobutyric Acid - metabolism
Male
Motor Activity - drug effects
Nerve Tissue Proteins - metabolism
Rats
Rats, Inbred Strains
Receptors, Cell Surface - drug effects
Receptors, Dopamine - drug effects
Receptors, GABA-A
Spiperone - metabolism
Vigabatrin
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Summary:Rat brain GABA levels were elevated chronically by daily administration of gamma-vinyl GABA, an enzyme-activated, irreversible inhibitor of GABA:2-oxo-glutarate aminotransferase (GABA-T; EC2.6.1.19). Following various periods of drug treatment and withdrawal, the sensitivity of dopamine and GABA receptors in the CNS was determined by biochemical and behavioral evaluations. In contrast to chronic haloperidol treatment, none of the treatment schedules with gamma-vinyl GABA had any significant effect on parameters such as apomorphine induced locomotor activity, [3H] spiperone binding or dopamine-stimulated adenylate cyclase in the corpus striatum; nor did gamma-vinyl GABA treatment affect [3H] GABA binding or GABA-activated [3H] diazepam binding in the cerebral cortex. Moreover, co-administration of gamma-vinyl GABA and haloperidol did not alter the ability of the neuroleptic to induce supersensitivity in the striatal dopaminergic system. Thus, it appears that, in contrast to reported studies using chronic administration of other less specific GABA-T inhibitors such as gamma-acetylenic GABA, amino-oxyacetic acid and isonicotinic acid hydrazide or direct GABA agonists such as THIP (4,5,6,7-tetrahydroisoxazolo (5,4-c-)-pyridin-3-ol) or kojic amine, gamma-vinyl GABA does not alter the sensitivity of the striatal dopaminergic system.
ISSN:0033-3158
DOI:10.1007/BF00427799