Release of vasopressin and oxytocin by excitatory amino acid agonists and the effect of antagonists on release by muscarine and hypertonic saline, in the rat in vivo.

1. It has been claimed that glutamate is the dominant excitatory neurotransmitter in neuroendocrine regulation. The evidence is derived mainly from in vitro experiments. 2. We have investigated in vivo a possible role of excitatory amino acids (EAAs) in the neural control of release of vasopressin (AVP) and oxytocin from the neurohypophysis. 3. In rats under ethanol anaesthesia in which a diuresis was maintained by a constant fluid load, the i.c.v. injection of glutamate and the synthetic agonists alpha-amino, 3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA) produced an antidiuretic response (ADR) which was abolished by an AVP antagonist. For AMPA and NMDA it was shown that this ADR was accompanied by increased urinary excretion of AVP and oxytocin. 4. The selectivity of antagonists was tested in this system. D-2-Amino-5-phosphonopentanoate (D-AP5) blocked the responses to NMDA but not to AMPA; 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) blocked the responses to both agonists. 5. The ADR to muscarine and hypertonic saline i.c.v., and the increase in excretion of AVP and oxytocin in response to muscarine, were blocked by CNQX but not by D-AP5. 6. The results suggest that hypertonic saline releases AVP and muscarine releases both AVP and oxytocin, at least in part, by activating a glutaminergic input to the SON and PVN involving an AMPA receptor. This input could function as a terminal interneurone in afferent neural pathways to these nuclei.