SDZ-216-525, A SELECTIVE 5-HT1(A) RECEPTOR ANTAGONIST, REVERTS ZINC-INDUCED INHIBITION OF WATER-INTAKE IN DEHYDRATED RATS

Zinc is found in many brain regions where it participates in important processes such as neurotransmission and neuromodulation. We previousl y demonstrated that acute third ventricle injection of zinc inhibits w ater intake in dehydrated rats. The present study was undertaken to ex plore a possible link between zinc-induced inhibition of water intake in dehydrated rats and serotonergic systems in the brain. Adult, male Wistar rats had the third ventricle cannulated a week before the exper iments. After an overnight period of water deprivation, the animals (N = 12 per group) received acute intracerebroventricular injections (2 mu l) of Zn(Ac)(2) (6.7, 67.1 and 671.6 ng/rat), Control animals (N = 12) received NaAc (671.6 ng/rat). Zinc-treated animals displayed a sig nificant, dose-dependent reduction in water intake, Water intake after 120 min was 7.70 +/- 0.50 ml in control (NaAc-treated) dehydrated rat s while animals treated with the highest dose of Zn(Ac)(2) drank 2.63 +/- 0.73 ml. Third ventricle injections of SDZ 216-525, a selective 5H T1(A) receptor antagonist, 45 min before zinc administration, generate d a dose-dependent reversal of zinc-induced thirst blockade in water-d eprived rats. At the highest dose used (10 mu g/rat), the water intake of the animals after 120 min was 7.30 +/- 0.23 ml, a value equal to t hat of control animals. These data suggest that zinc may decrease wate r intake in dehydrated rats by activation of a 5-HT1(A) receptor-relat ed mechanism.