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

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Abstract

Rat brain GABA levels were elevated chronically by daily administration of γ-vinyl GABA, an enzyme-activated, irreversible inhibitor of GABA:2-oxo-gluaarate aminotransferase (GABA-T; EC 2.6.1.19). 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 γ-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 γ-vinyl GABA treatment affect [3H] GABA binding or GABA-activated [3H] diazepam binding in the cerebral cortex. Moreover, co-administration of γ-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 γ-acetylenic GABA, amino-oxyacetic acid and isonicotinic acid hydrazide or direct GABA agonists such as THIP (4,5,5,7-tetrahydroisoxazolo (5,4-c-)-pyridin-3-ol) or kojic amine, γ-vinyl GABA does not alter the sensitivity of the striatal dopaminergic system.

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Author notes

  1. Colin R. Gardner

    Present address: Merck Sharp and Dohme research Laboratories, INTERx Research Corporation, Lawrence, Kansas, USA

Authors and Affiliations

  1. Centre de Recherche Merrell International, 16, rue d'Ankara, F-67084, Strasbourg Cedex, France

    Colin R. Gardner, Pierre Mallorga, Josiane Klein, Sylvie Huot-Olivier & Michael G. Palfreyman

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  1. Colin R. Gardner
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  2. Pierre Mallorga
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  3. Josiane Klein
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  4. Sylvie Huot-Olivier
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  5. Michael G. Palfreyman
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Gardner, C.R., Mallorga, P., Klein, J. et al. Chronic elevation of brain GABA by γ-vinyl GABA treatment does not alter the sensitivity of GABAergic or dopaminergic receptors in rat CNS. Psychopharmacology 79, 130–136 (1983). https://doi.org/10.1007/BF00427799

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