Differential modulation of angiotensin II and hypertonic saline-induced drinking by opioid receptor subtype antagonists in rats.

Opioid modulation of ingestion includes general opioid antagonism of different forms of water intake, mu 2 receptor modulation of deprivation-induced water intake and delta 2 receptor modulation of saccharin intake. Water intake is stimulated by both central administration of angiotensin II (ANG II) and peripheral administration of a hypertonic saline solution; both responses are reduced by general opioid antagonists. The present study examined whether specific opioid receptor subtype antagonists would selectively alter each form of water intake in rats. Whereas systemic naltrexone (0.1-2.5 mg/kg, s.c.) reduced water intake induced by either peripheral ANGII (500 micrograms/kg, s.c.) or hypertonic saline (3 ml/kg, 10%), intracerebroventricular (i.c.v.) naltrexone (1-50 micrograms) only inhibited central ANGII (20 ng)-induced hyperdipsia. Both forms of drinking were significantly and dose-dependently inhibited by the selective kappa antagonist, nor-binaltorphamine (Nor-BNI, 1-20 micrograms). Whereas both forms of drinking were transiently reduced by the mu-selective antagonist, beta-funaltrexamine (beta-FNA, 1-20 micrograms), the mu 1 antagonist, naloxonazine (40 micrograms) stimulated drinking following hypertonic saline. The delta 1 antagonist, [D-Ala2, Leu5, Cys6]-enkephalin (DALCE, 1-40 micrograms) significantly reduced drinking following ANGII, but not following hypertonic saline; the delta antagonist, naltrindole failed to exert significant effects. These data indicate that whereas kappa opioid binding sites modulate hyperdipsia following hypertonic saline, mu 2, delta 1, and kappa opioid binding sites modulate hyperdipsia following ANGII. The mu 1 opioid binding site may normally act to inhibit drinking following saline.