SDZ 216-525, a selective 5-HT1A 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 previously demonstrated that acute third ventricle injection of zinc inhibits water intake in dehydrated rats. The present study was undertaken to explore 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 experiments. After an overnight period of water deprivation, the animals (N = 12 per group) received acute intracerebroventricular injections (2 microliters) 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 significant, dose-dependent reduction in water intake. Water intake after 120 min was 7.70 +/- 0.50 ml in control (NaAc-treated) dehydrated rats 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 5-HT1A receptor antagonist, 45 min before zinc administration, generated a dose-dependent reversal of zinc-induced thirst blockade in water-deprived rats. At the highest dose used (10 micrograms/rat), the water intake of the animals after 120 min was 7.30 +/- 0.23 ml, a value equal to that of control animals. These data suggest that zinc may decrease water intake in dehydrated rats by activation of a 5-HT1A receptor-related mechanism.