The ethanol withdrawal syndrome: A role for dihydropyridine-sensitive calcium channels in neuronal hyperexcitability states
This project investigated the effects of dihydropyridine calcium channel blockers on behavioral and electrophysiological aspects of ethanol withdrawal. The effects of the dihydropyridine (+)-PN 200-110, on changes in neuronal function during ethanol withdrawal, were compared with effects on changes caused by the GABAergic convulsant drug bicuculline. Behavioral correlates of ethanol withdrawal were measured in two strains of mice using a rating of handling-induced convulsions. Concurrent chronic treatment with ethanol and the dihydropyridine calcium channel blockers ([plus minus])-nitrendipine, ([plus minus])-nimodipine or ([plus minus])-PN 200-110 prevented withdrawal-induced increased in convulsive behavior. This effect was dose dependent. The duration of chronic treatment with calcium channel blocker affected the degree of protection against increases in convulsive behavior seen during ethanol withdrawal. Concurrent chronic treatment with ethanol, and the mixed calcium channel activator/blocker ([plus minus])-BAY K 8644, prevented ethanol withdrawal-induced increases in convulsive behavior. Single acute injections of nitrendipine immediately on cessation of chronic treatment with ethanol, or 2h later, reduced withdrawal-induced increases in convulsive behavior in a dose-dependent manner throughout the 12h test period. Slices isolated from mice after chronic ethanol treatment showed a complex, time-dependent pattern of changes in the above measurements, culminating in epileptiform discharges seen from 4h to 7h into withdrawal.
- Research Organization:
- Bristol Univ. (United Kingdom)
- OSTI ID:
- 7175448
- Resource Relation:
- Other Information: Thesis (Ph.D.). Order No. BRD-94,078
- Country of Publication:
- United States
- Language:
- English
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ENZYME INHIBITORS
BIOLOGICAL EFFECTS
ETHANOL
TOXICITY
NERVE CELLS
BIOLOGICAL FUNCTIONS
PORINS
CHRONIC INTAKE
COMPARATIVE EVALUATIONS
ELECTROPHYSIOLOGY
EXPERIMENTAL DATA
MICE
TIME DEPENDENCE
ALCOHOLS
ANIMAL CELLS
ANIMALS
DATA
EVALUATION
HYDROXY COMPOUNDS
INFORMATION
INTAKE
MAMMALS
MEMBRANE PROTEINS
NUMERICAL DATA
ORGANIC COMPOUNDS
PHYSIOLOGY
PROTEINS
RODENTS
SOMATIC CELLS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology