INTERACTIONS BETWEEN N-METHYL-D-ASPARTATE, NITRIC-OXIDE AND SEROTONININ THE CONTROL OF PROLACTIN SECRETION IN PREPUBERTAL MALE-RATS

The role of N-methyl-D-aspartate (NMDA) in the control of prolactin (P RL) secretion was analysed in prepubertal male rats. In experiment 1, males of different ages were decapitated after administration of NMDA or vehicle. In experiment 2, 30-day-old males were killed at different times after administration of vehicle, NMDA, MK-801 (a non-competitiv e NMDA antagonist) or NMDA plus MK-801. In experiment 3, 23-day-old ma les were sham-orchidectomized or orchidectomized. Orchidectomized male s were or were not implanted with Silastic capsules containing differe nt amounts of testosterone. On day 30, the animals were decapitated af ter administration of vehicle, NMDA or MK-801. In experiment 4, 30-day -old male rats were decapitated after being injected with vehicle, NMD A, N-w-nitro-L-arginine methyl ester (NAME) (an inhibitor of nitric ox ide (NO) synthase), or NMDA plus NAME. Serum PRL concentrations, and d opamine pituitary and hypothalamic content were measured. In experimen t 5, males pretreated with vehicle or NAME were killed after administr ation of the precursor of serotonin synthesis 5-hydroxytryptophan (5-H TP), the 5-HT1 receptor agonist 8-hydroxy-2-(di-n-propylamino) tetrali n (8-OH-DPAT) or the 5-HT2 agonist (+/-)2,5-dimethoxy-4-iodoamphetamin e hydrochloride (DOI). Finally, the effects of NMDA, NAME and sodium n itroprusside (SNP) were tested in dispersed adenohypophyseal cells. We found that: (i) antagonism of NMDA receptors with MK-801 decreased PR L secretion in intact, orchidectomized and orchidectomized-testosteron e treated male rats; (ii) NMDA inhibited PRL release in vivo through a n increase in dopamine release and this effect was potentiated by NAME and prevented by testosterone; (iii) NMDA inhibited PRL secretion in vitro and this effect was observed in presence of both SNP and NAME; ( iv) NAME blocked the stimulatory effects of 5-HTP and DOI on PRL secre tion. We conclude that endogenous glutamate stimulates PRL release and that NO might have a pivotal role in the mechanisms involved in the c ontrol of PRL release, inhibiting the release of dopamine and modulati ng the effects of NMDA and 5-HT.