Gonadotropin-releasing hormone (GnRH) as antidepressant: a psychopharmacological animal study

Because the secretion of gonadotrophic hormones is disturbed in some depressive states, it has been hypothesized that gonadotropin-releasing hormone (GnRH) has antidepressant properties in humans, but no clear information has emerged from clinical trials. The lack of experimental psychopharmacological data prompted us to investigate the effects of GnRH on the 'learned helplessness' behavioral model of depression in rats. GnRH was injected i.p. at doses of 0.06, 0.25, 0.50, 1 and 2 mg/kg per day. GnRH significantly reduced the number of escape failures at doses of 1 mg/kg per day or higher during the first shuttle-box session and at doses of 0.25 mg/kg per day onwards during the third shuttle-box session. These antidepressant-like effects of GnRH were similar to those observed with the tricyclic antidepressants imipramine (32 mg/kg per day) or clomipramine (32 mg/kg per day) in the same model. Moreover, while the induction of learned helplessness behaviour resulted in a fall in the plasma levels of FSH and LH, normal values of these hormones could be restored by a behaviorally effective GnRH regimen. From these data it can be suggested that GnRH exhibits an interesting antidepressant-like activity in rats.