The gabaergic hypothesis of depression

doi:10.1016/0278-5846(89)90123-1

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volume 13, Issues 3–4, 1989, Pages 341-351

https://doi.org/10.1016/0278-5846(89)90123-1 Get rights and content

Abstract

1. GABAergic mechanisms have been generally ignored in the study of mood disorders and antidepressant drug (AD) action. Recently data have accumulated indicating that GABAergic mechanisms may be involved in both of these.

2. Mood disorders: GABA levels are reported to be low in the CSF and plasma of depressed patients and are related to mood changes. GABA_B receptors are decreased in the frontal cortex in two rodent behavioral models of depression and GABA release is reported diminished in the hippocampus. GABAergic drugs (progabide, fengabine) reverse the behavioral deficits in the rodent models and exert clear therapeutic effects in depressed patients.

3. AD action: In behavioral models imipramine upregulates GABA_B receptors only in those animals which respond behaviorally to the AD. In naive rats repeated administration of varied ADs upregulates GABA_B receptors in the frontal cortex whereas non-ADs (including amphetamine) do not. Bicuculline inhibits the action of imipramine in the learned helplessness model. GABA_A receptor stimulation enhances noradrenaline release in the ventral NA pathway.

4. Conclusions: GABAergic mechanisms likely play a role in the modulation of mood and increasing GABAergic tone exerts an antidepressant effect. Actions at GABA synapses appear to be a fundamental facet of ADs, perhaps together with ß-adrenoceptor mediated events.

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The gabaergic hypothesis of depression

Abstract

Neurosci. Lett.

Eur. J. Pharmacol.

Prog. Neuro-Psychopharmacol. Biol. Psychiat.

Pharroacol. Biochem. Behav.

Brain Res. Bull.

Brain Res.

J. Neurol. Sci.

Life Sci.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Maprotiline: an antidepressant with an unusual pharmacological profile

J. Pharmacol. Exp. Ther.

GABA and Hood Disorders: Experimental and Clinical Research

On the mode of action of SL 76002, a new GABA receptor agonist

Functional evidence for altered activity of gabaergic receptors following chronic desipramine treatment in rats

J. Pharm. Pharmacol.

Plasma GABA: a potential indicator of altered GABAergic function in psychiatric illness

GABAB binding sites in the cortex and hippocampus of depressed suicide victims

Br. J. Pharmac.

Influence of baclofen and GABA-mimetic agents on spontaneous and olfactory-bulb-ablation-induced muricidal behaviour in the rat

Arzneimitkel-Forsch.

GABAB agonists and imipramine-induced modifications in rat brain β-adrenergic receptor binding and function

CSF neurochemistry discriminate function analysis of GABA, HVA, MHPG, 5-HIAA, cortisol, SRIF, BBS and CCK among normals, depressed, manic, schizophrenic and anorexic subjects

Hypothermia induced by baclofen, a possible index of GABAB receptor function in mice, is enhanced by antidepressant drugs and ECS

Br. J. Pharmac.

Increased GABAB receptor function in mouse frontal cortex after repeated administration of antidepressant drugs or electroconvulsive shocks

Br. J. Pharmae.

GABA_B binding sites in the cortex and hippocampus of depressed suicide victims

GABA_B agonists and imipramine-induced modifications in rat brain β-adrenergic receptor binding and function

Hypothermia induced by baclofen, a possible index of GABA_B receptor function in mice, is enhanced by antidepressant drugs and ECS

Increased GABA_B receptor function in mouse frontal cortex after repeated administration of antidepressant drugs or electroconvulsive shocks