Biochemical and behavioral evidence for an interaction between ethanol and calcium channel antagonists

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Abstract
Summary In the present series of experiments we have studied the effects of the dihydropyridine calcium channel antagonist nifedipine on ethanol-induced changes in behavior and dopamine (DA) release and metabolism. The locomotor-stimulatory effect of low doses of ethanol (2.5 g/kg) was antagonized by nifedipine, whereas ethanol-induced sedation observed after higher doses (4.5 g/ kg) was potentiated. Biochemical studies indicated that ethanol enhanced the metabolism and release of DA in the striatum and the DA-rich limbic regions measured by post mortem analyses of DA-metabolites by HPLC with electrochemical detection and by in vivo voltammetry in anaesthetized rats, respectively. Pretreatment with nifedipine antagonized the stimulatory effects of ethanol on the DA-system. Nifedipine reduced the preference for ethanol, estimated by the relative intake of ethanol (6% v/v) and water in a free-choice situation, suggesting an influence of nifedipine not only on the stimulatory but also on the positive reinforcing effects of ethanol. The present results suggest that the locomotor-stimulatory and positive reinforcing effects of ethanol as well as its enhancing effect on dopaminergic activity may involve an enhancement of calcium mediated mechanisms.

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