TIME-COURSE AND GENETIC-VARIATION IN THE REGULATION OF CALCIUM-CHANNEL ANTAGONIST BINDING-SITES IN RODENT TISSUES DURING THE INDUCTION OF ETHANOL PHYSICAL-DEPENDENCE AND WITHDRAWAL

GUPPY LJ CRABBE JC LITTLETON JM

Lj. Guppy et al., TIME-COURSE AND GENETIC-VARIATION IN THE REGULATION OF CALCIUM-CHANNEL ANTAGONIST BINDING-SITES IN RODENT TISSUES DURING THE INDUCTION OF ETHANOL PHYSICAL-DEPENDENCE AND WITHDRAWAL, Alcohol and alcoholism, 30(5), 1995, pp. 607-615

30

INGLESE

Article

Substance Abuse

Alcohol and alcoholism → ACNP

0735-0414

30

5

1995

607 - 615

ISI

0735-0414(1995)30:5<607:TAGITR>2.0.ZU;2-U

Physical dependence was induced by ethanol inhalation in male Sprague- Dawley rats and, in parallel experiments, in two lines of mice (WSR an d WSP) genetically selected for differential severity of ethanol withd rawal. In dependent rats [H-3]nitrendipine binding sites were signific antly increased in cerebral cortex, cardiac and smooth muscle (vas def erens). Cerebral cortical membranes were the first to show an increase , the B-max for nitrendipine binding rising sharply after 3-4 days of ethanol administration, whereas binding sites in the other tissues inc reased after 5-6 days. Nitrendipine binding affinity in all tissues wa s consistently reduced immediately preceding the rise in B-max to a ne w steady state, but then returned to control values. Between 6 and 10 days of ethanol exposure there was no further increase in the B-max fo r nitrendipine binding, and on removal of ethanol, the numbers of nitr endipine binding sites fell precipitously to control levels within 24 h of withdrawal. In the genetically selected mice, the up-regulation o f nitrendipine binding sires in cardiac membranes was significantly gr eater in the WSP line. This correlates with severity of physical signs of withdrawal and parallels previous results obtained in brain. The r esults are consistent with an increase in the synthesis and membrane i nsertion of dihydropyridine sensitive calcium channel proteins in seve ral tissues during the induction of ethanol dependence and suggest tha t in the brain this change may play a role in the ethanol withdrawal s yndrome.