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J Pharmacol. 1985;16 Suppl 2:5-27.

[Implications of GABAergic synapses in neuropsychiatry].

[Article in French]


The use of a multidisciplinary approach--laboratory and clinical pharmacology and experimental and human neurochemistry--has demonstrated that GABA neurons and receptors play a variety of functional roles in the mammalian brain. The present synopsis has been limited to some of the newer aspects of GABA neuron function. Thus there is strong evidence that GABA neurons are involved in the control of cerebral excitability (cf. tables I, II) and in the genesis of at least some seizures states, including certain types of human epilepsy (table III). Furthermore GABA receptor activation can be used to control seizures of diverse etiology and at least one GABA agonist, progabide, is effective in human epilepsy. There is a foundation for the belief that GABA neurons function in the control of affect and emotion. The most convincing evidence is from laboratory and clinical pharmacology studies in depression and models for the development of new antidepressant drugs. GABA agonists act as antidepressants not only in animal models such as learned helplessness, olfactory bulbectomy and the sleep-cycle but also demonstrate an antidepressant action in man. Additionally, the recent studies showing that chronic treatment by antidepressants, induce an increase in 3H-GABA "B" binding strongly support a GABAergic contribution in the mechanism of antidepressant drugs (cf. table IV). There is also some evidence for the hypothesis that GABA neurons and receptors participate in the biology of anxiety, or at least the mechanism of action of anxiolytics. This is based mainly on the known molecular pharmacology of the benzodiazepine receptor and the evidence in animal models for anxiety (table V). However in clinical trials the GABA agonist progabide is only a weak anxiolytic. A major function of GABA neurons and receptors is the regulation of the nigro-striatal dopamine pathway (table VI) and the expression of dopamine receptor mediated events (table VII). This modulation probably occurs via at least 3 mechanisms: a tonic inhibition of dopamine neuron activity regulating dopamine synthesis, turnover and release; a long term modulation controlling striatal dopamine receptor numbers, modification of the expression of dopaminergic transmission distal to the dopaminergic synapse.

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