Repeated moderate-dose ethanol bouts impair cognitive function in Wistar rats.
The effects of repeated, intermittent administration of a moderate dose of ethanol (3.4 g/kg/day × 6 days, intragastrically via gavages) on cognitive function were examined in male Wistar rats. No significant differences in weight gain between the ethanol- and water-treated rats were found. Analysis of physical dependence revealed no signs of spontaneous withdrawal, whereas withdrawal signs exacerbated by Ro15-4513, an inverse benzodiazepine agonist, were apparent 5 hours but not 24 hours after the cessation of ethanol treatment. Spatial learning and memory, as assessed in the Barnes maze, were impaired 3-6 days following the treatment but recovered by the 11th-14th days. Reversal learning, however, was impaired throughout the 2-week observation period. Thus, bouts of moderate-dose ethanol administration transiently impair spatial learning and memory, and promote cognitive inflexibility. The employed ethanol exposure paradigm may provide a model of human cognitive deficits associated with alcohol binge drinking.
Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences, Uppsala University, Sweden.
Alexander
A
Kuzmin
Sture
S
Liljequist
Jennifer
J
Meis
Vladimir
V
Chefer
Toni
T
Shippenberg
Georgy
G
Bakalkin
D000428:Alcohol Drinking / Q000009:adverse effects*; D000704:Analysis of Variance; D000818:Animals; D001386:Azides; D001569:Benzodiazepines; D002492:Central Nervous System Depressants / Q000633:toxicity*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome; D013997:Time Factors; D014867:Water / Q000008:administration & dosage
D001386:Azides; D002492:Central Nervous System Depressants; D014867:Water; D001569:Benzodiazepines; D000431:Ethanol; C042957:Ro 15-4513