title: GABA and affective disorders.
abstract: Recently sufficient evidence has accumulated to propose that a central GABAergic dysfunction may be primarily related to the pathology of affective disorders and that antidepressant mechanisms (pharmacological or electroconvulsive therapy, ECT) have an intrinsic GABAergic component. In depressed patients GABA levels are reported to be low in the CSF and plasma, and GABA synthesis is decreased in some brain areas, including the frontal cortex. GABAmimetics such as progabide and fengabine exert a therapeutic effect in depression. In behavioural laboratory models GABAmimetics exhibit antidepressant-like actions in the olfactory bulbectomized rat and in rats submitted to an inescapable shock (learned helplessness). Furthermore, antidepressant GABAmimetics decrease paradoxical sleep. In the olfactory bulbectomized rat, GABAB receptors are downregulated in the frontal cortex and in the learned helplessness model, GABA release is diminished in the hippocampus. These decreases are reversed by antidepressants in parallel with their behavioural activities. An intrinsic activity of widely varied antidepressants and ECT is the upregulation of GABAB receptors in the frontal cortex. This, together with the downregulation of beta-adrenergic receptors induced by these compounds, and the GABAB modulation of the beta-adrenergic second messenger system, strongly suggest that both GABAergic and beta-adrenergic responses are inherent to an antidepressant effect.
authors.affiliation: Laboratories D'Etudes et de Recherches Synthelabo (L.E.R.S.), Bagneux, France.
authors.forename: K G
authors.initials: KG
authors.lastname: Lloyd
authors.forename: P L
authors.initials: PL
authors.lastname: Morselli
authors.forename: G
authors.initials: G
authors.lastname: Bartholini
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D019964:Mood Disorders / Q000188:drug therapy / Q000503:physiopathology*; D011963:Receptors, GABA-A / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D000928:Antidepressive Agents; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid