GABAergic hypotheses of anxiety and depression: focus on GABA-B receptors

Depression and anxiety are psychiatric disorders with high morbidity and comorbidity. Because of multiple adverse effects of existing drugs and a low efficacy, therapy for a substantial number of patients is unsatisfactory. It is widely accepted that gamma-aminobutyric acid (GABA) is the primary inhibitory transmitter substance in the mammalian central nervous system. Data are accumulating that the recently cloned GABAB receptors might become a target for the development of new antidepressant and/or anxiolytic drugs. The existing data support the hypothesis that agonists and particularly positive modulators of GABAB receptors (but not GABAB receptor antagonists) may be anxiolytic drugs in the future. The experiments demonstrate that the most consistent finding following chronic administration of antidepressants is an increase in GABAB receptor function, with or without a change in receptor binding or subunit expression. Data are accumulating in preclinical studies that show that antagonists (but not agonists) of GABAB receptors may have antidepressant effects.