RELEASE OF VASOPRESSIN AND OXYTOCIN BY EXCITATORY AMINO-ACID AGONISTSAND 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 neurot ransmitter in neuroendocrine regulation. The evidence is derived mainl y from in vitro experiments. 2 We have investigated in vivo a possible role of excitatory amino acids (EAAs) in the neural control of releas e of vasopressin (AVP) and oxytocin from the neurohypophysis. 3 In rat s under ethanol anaesthesia in which a diuresis was maintained by a co nstant 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 (A DR) 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 hy pertonic saline i.c.v., and the increase in excretion of AVP and oxyto cin 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 glu taminergic input to the SON and PVN involving an AMPA receptor. This i nput could function as a terminal interneurone in afferent neural path ways to these nuclei.