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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AA008182-03
Application #
2044344
Study Section
Biochemistry, Physiology and Medicine Subcommittee (ALCB)
Project Start
1990-04-01
Project End
1994-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260