Nimodipine prior to alcohol withdrawal prevents memory deficits during the abstinence phase.
Effects of the dihydropyridine, nimodipine, an antagonist at L-type calcium channels, on the memory loss in rats caused by long term alcohol consumption were examined. Either a single dose of nimodipine or 2 weeks of repeated administration was given prior to withdrawal from 8 months of alcohol consumption. Memory was measured by the object recognition test and the T maze. Both nimodipine treatments prevented the memory deficits when these were measured between 1 and 2 months after alcohol withdrawal. At the end of the memory testing, 2 months after cessation of chronic alcohol consumption, glucocorticoid concentrations were increased in specific regions of rat brain without changes in plasma concentrations. Both nimodipine treatment schedules substantially reduced these rises in brain glucocorticoid. The data indicate that blockade of L-type calcium channels prior to alcohol withdrawal protects against the memory deficits caused by prolonged alcohol intake. This shows that specific drug treatments, such as nimodipine, given over the acute withdrawal phase, can prevented the neuronal changes responsible for subsequent adverse effects of long term consumption of alcohol. The results also suggest the possibility that regional brain glucocorticoid increases may be involved in the adverse effects of long term alcohol intake on memory. Such local changes in brain glucocorticoid levels would have major effects on neuronal function. The studies indicate that L-type calcium channels and brain glucocorticoid levels could form new targets for the treatment of cognitive deficits in alcoholics.
School of Biosciences, Park Place, Cardiff University, CF10 3XT, UK.
S P
SP
Brooks
A P
AP
Croft
G
G
Norman
S G
SG
Shaw
H J
HJ
Little
D020751:Alcohol-Induced Disorders; D000438:Alcohols / Q000009:adverse effects; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D003345:Corticosterone / Q000378:metabolism; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D008297:Male; D008569:Memory Disorders / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D009483:Neuropsychological Tests; D009553:Nimodipine / Q000008:administration & dosage*; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000150:complications* / Q000209:etiology
D000438:Alcohols; D002121:Calcium Channel Blockers; D009553:Nimodipine; D003345:Corticosterone