GABA, DEPRESSION AND THE MECHANISM OF ACTION OF ANTIDEPRESSANT DRUGS - A NEUROENDOCRINE APPROACH

Recent evidence has suggested the involvement of the GABAergic system in depression and in the mechanism of action of somatic antidepressant treatments. In particular, GABAB receptors have been found to be increased in the rat frontal cortex following chronic antidepressant therapies. In the present study, the sensitivity of GABAB binding sites was assessed in nine healthy men and 10 depressed patients via the plasma growth hormone (GH) response to acute baclofen administration (20 mg p.o.). Depressed subjects were tested before and after 15 and 35 days of treatment with amitriptyline (100 mg/day), imipramine (100 mg/day) and fluoxetine (20 mg/day). GH response to acute GABAB receptor activation did not differ between depressed subjects and healthy controls. Moreover, chronic antidepressant treatment did not significantly modify this response, even when a clear therapeutic effect was obtained. These results do not support the idea that GABAergic mechanisms are involved in the pathophysiology of depression and in the mechanism of action of antidepressant drugs. © 1990.