The roles of posterior and anterolateral connections to the mediobasal hypothalamus (MBH) as well as innervation of the posterior pituitary in the PRL response to immobilization (IMO) and hemorrhage (HEM) were studied by means of surgical isolation, performed 6-9 days before stress exposure. Male rats bearing indwelling tail artery cannulae subjected to 120-min IMO reached peak PRL secretion in 5-20 min. HEM of 25% elicited a significant rise of PRL levels. A posterior cut in the MBH, performed without damaging the serotonergic fibers from the brain stem, attenuated the PRL response to 25% HEM, whereas the PRL elevation due to IMO remained unaffected. An anterolateral cut around the MBH eliminated both the IMO- and HEM-induced stimulation of PRL. Posterior lobe denervation reduced by about 27% the PRL response to IMO and eliminated the response to HEM. These results suggest the following conclusions. The neural structures located posteriorly to the MBH are involved in the transfer of signals triggering PRL secretion due to hypovolemia. Intact anterolateral pathways to the MBH and stalk-median eminence region are essential for the PRL-releasing activity under both stimuli. The posterior lobe may be an important link in the PRL stress response in male rats.

The effect of N-methyl-D-aspartic acid (NMDA) receptor blockade on adrenocorticotropin (ACTH) and catecholamine activation during stress was investigated in conscious rats with indwelling catheters for both blood sampling and drug treatment. Secretion of ACTH in response to immobilization stress (20 min) was inhibited by pretreatment (20 min before stress exposure) with the centrally acting noncompetitive antagonist of NMDA receptors MK-801 (dizocilpine, the racemic form, 1 mg/kg i.p.) but not by 3-[( ± )-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid (CPP; 10 mg/kg i.p.), a competitive NMDA receptor antagonist. Administration of MK-801 (1 mg/kg i.p.) inhibited norepinephrine and totally prevented epinephrine response during acute immobilization stress. Pretreatment with a low dose of MK-801 (0.1 mg/kg i.p.) failed to modify basal or stress-induced ACTH and catecholamine release. The stress-induced rise in plasma epinephrine was found to be attenuated by the peripherally injected competitive antagonist CPP (10 mg/kg i.p.) suggesting that modulation not only of central but also of peripheral NMDA receptors may come into play. Our results indicate the involvement of endogenous excitatory amino acids in the control of ACTH and particularly of epinephrine secretion during stress.