Effects of central administration of gonadotropin-releasing hormone agonists and antagonist on elevated plus-maze and social interaction behavior in rats.

The correlation between neuronal mechanism of anxiety and neuroanatomic expression/neuromodulatory role of gonadotropin-releasing hormone (GnRH), points to a role of GnRH in the modulation of anxiety. Therefore, we investigated the influence of GnRH agonists and antagonist on the anxiety-like behavior of rats in the elevated plus-maze and social interaction tests. GnRH agonists, leuprolide [100 or 200 ng/rat, intracerebroventricularly (i.c.v.)] or 6-D-tryptophan luteinizing hormone-releasing hormone (400 ng/rat, i.c.v.), significantly increased percentage of open arms entries, time spent in open arms, and time spent in social interaction. The observed anxiolytic effect of these agents was comparable with diazepam (0.5-1.0 mg/kg, intraperitoneally). Treatment with a GnRH antagonist [pGlu-D-Phe-Trp-Ser-Tyr-D-Ala-Leu-Arg-Pro-Gly-NH2, (100 ng/rat, i.c.v.)], significantly reduced percentage of open arm indices and decreased time spent in social interaction, indicating an anxiogenic-like effect. Further, castrated rats exhibited anxiogenic-like behavior in these tests, which was significantly attenuated by leuprolide (200 ng/rat, i.c.v.) or 6-D-tryptophan luteinizing hormone-releasing hormone (400 ng/rat, i.c.v.), indicating the noninvolvement of peripheral sex hormone in their anxiolytic-like effect, at least in castrated rats. In conclusion, this study indicated a putative role of GnRH in the control of anxiety, and further adds to the importance of investigating the possible role of the hypothalamus-pituitary-gonadal axis in regulating the anxiety-related disorders arising out of hypothalamus-pituitary-adrenal axis dysregulation.