ALTERATIONS IN 8-HYDROXY-2-(DIPROPYLAMINO)TETRALIN-INDUCED NEUROENDOCRINE RESPONSES AFTER 5,7-DIHYDROXYTRYPTAMINE-INDUCED DENERVATION OF SEROTONERGIC NEURONS

In the present study, we examined denervation-induced changes in the s ensitivity of hypothalamic postsynaptic serotonin(1A) (5-HT1A) recepto r function with respect to changes in the dose-dependent elevation in plasma hormones [adrenocorticotropic hormone (ACTH), corticosterone, p rolactin, oxytocin, prolactin, renin and vasopressin] by the 5-HT1A ag onist 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT). Rats received i ntracerebroventricular (i.c.v.) injections of the serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) or vehicle (0.1% ascorbate in salin e) 3 weeks before challenge with increasing doses of 8-OH-DPAT (0, 10, 50 or 200 mu g/kg s.c.). The effectiveness of 5,7-DHT-induced destruc tion of serotonergic neurons was confirmed by a 93% reduction in [H-3] paroxetine-labeled 5-HT uptake sites in the hypothalamus. No changes i n basal levels of ACTH, corticosterone, oxytocin, prolactin, renin and vasopressin were observed in rats that received i.c.v. 5,7-DHT inject ions. The dose-response curves for 8-OH-DPAT-induced elevations of pla sma corticosterone and prolactin levels were shifted to the left in ra ts treated with 5,7-DHT, whereas no significant difference in the ACTH dose-response curve was observed between rats treated with vehicle an d rats treated with 5,7-DHT. In contrast, the maximal oxytocin respons e to 8-OH-DPAT was attenuated in rats treated with 5,7-DHT. A 5,7-DHT- induced decline in the synthesis of oxytocin could explain this phenom enon. Although 8-OH-DPAT did not increase plasma levels of renin or va sopressin in rats treated with vehicle, 8-OH-DPAT produced an elevatio n (75%) in plasma renin concentration but not in vasopressin levels in rats that received i.c.v. injections of 5,7-DHT. No change was observ ed in [H-3]8-OH-DPAT labeled 5-HT1A receptors in the hypothalamus. In summary, denervation of hypothalamic serotonergic nerve terminals prod uces supersensitivity of some neuroendocrine responses to 8-OH-DPAT in dependent of changes in the density of hypothalamic 5-HT1A receptors.