Although the cellular and molecular mechanism by which alcohol produces its sedative, hypnotic and anaesthetic effects is as yet unclear, evidence suggests that an action on voltage dependent calcium channels (VDCCs) may be involved. This is supported by the observation that alcohol withdrawal symptoms are alleviated by dihydropyridines. The objectives of this proposal is to examine the effects of acute and chronic alcohol administration on the VDCC subtypes (L, N and T) and the consequences of any effects on transmitter release, both in adult animals and in the offspring of alcohol treated mothers. Using brain slices and synaptosomes form discrete brain areas including the hippocampus, cortex, striatum, hypothalamus, brain stem and cerebellum, the acute and chronic effects of alcohol on L and N channel will be determined with radioligand binding techniques. Using selective antagonists the effect of alcohol on channel subtypes mediating the release of [3H]-labeled acetylcholine, norepinephrine and GABA and on 45Ca2+ uptake from these brain areas will also be examined. Alcohol will be given chronically by pair feeding a liquid containing 6.5% alcohol for 3 weeks. Correlations will be sought between the effects of alcohol on channel activity and transmitter release. The data should enable the determination of which VDCC channel types are sensitive to alcohol and may be of value in determining the usefulness of VDCC antagonists other that dihydropyridines in the treatment of alcohol withdrawal.
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| Hawthorn, M H; Ferrante, J; Kwon, Y W et al. (1991) Drug actions and regulation at voltage-dependent neuronal Ca2+ channels (VDCCs). Ann N Y Acad Sci 635:413-5 |
