ATTENUATION OF DRINKING SWEETENED WATER FOLLOWING CALCIUM-CHANNEL BLOCKADE

Recent reports cite results that both cocaine-induced conditioned place preference and activity stimulation are attenuated by pretreatment with the calcium channel blocker isradipine (ISR) in rats. By blocking voltage-dependent L-type calcium channels. ISR may regulate neural dopamine release that. in turn. decreases the putative rewarding effects mediated by dopaminergic mechanisms. It is known that nonfluid deprived rats avidly consume sweetened fluids; this suggests that the sweet taste is rewarding. Three experiments were conducted to determine the effects of ISR on drinking sweetened and nonflavored water, Experiment 1 was designed to test whether ISR would attenuate the intake of a palatable solution in a dose-dependent manner. To this end, ISR was administered both peripherally (3.0-30 mg/kg) and centrally (0.3-30-mu-g/rat) prior to a solution of saccharin and d-glucose (S + G) being made available to rats (15 min/day) and intake was recorded. ISR produced dose-dependent decreases (38%-81%) in S + G intake dependent on the route of administration. In Experiment 2, water intake was measured in 18 h water-deprived rats following, ISR (10 mg/kg) administration as well as comparing S + G drinking. The effect of two ISR vehicles, dimethyl sulfoxide and Tween 80, upon fluid intake was also determined. ISR injection did not attenuate water intake in 18 h water-deprived rats and the choice of vehicle did not affect the ISR-induced attenuation of S + G drinking. In Experiment 3, a single dose (30-mu-g) of ICV administered ISR. that attenuated S + G intake by approximately 44%, did not attenuate water intake in 18 h water-deprived rats. Collectively, these findings demonstrate that ISR attenuates palatability-induced drinking that is believed to be regulated by neural dopaminergic systems. These findings suggest that calcium channel blockers may modulate brain reward mechanisms.