Benzodiazepine response and receptor binding after chronic ethanol ingestion in a mouse model

JG Barnhill, DA Ciraulo, DJ Greenblatt, MA Faggart and JS Harmatz

Department of Psychiatry, Tufts-New England Medical Center, Boston, Massachusetts.

Benzodiazepine receptor binding and open-field response were examined in male CD-1 mice after 6 weeks on a liquid diet providing either 36% ethanol or maltose-dextrin derived calories. In vivo binding of [3H]Ro15-1788, open-field activity and cortex and plasma concentrations were measured over a range of clonazepam doses (0.05-2.0 mg/kg). Mean +/- S.D. of ethanol consumption was 19.3 +/- 1.1 g/kg/day. Clonazepam concentration in plasma and cortex was related linearly to dose in both groups. Cortex concentrations exceeded plasma concentrations at all doses. Ethanol-consuming mice showed considerably less decrease in measures of horizontal and stereotypic activity at each dose studied. Mean in vivo IC50 was 20.9 +/- 4.0 ng/g for the control mice and 40.2 +/- 7.6 ng/g (P less than .001) in the ethanol-consuming mice. In vitro binding studies found a marked decrease in maximum binding in cortex (37%) with an increase in Kd (66%). Chronic ethanol can influence the acute effects of single doses of clonazepam and both in vivo and in vitro measures of benzodiazepine receptor binding.

Volume 258, Issue 3, pp. 812-819, 09/01/1991
Copyright © 1991 by American Society for Pharmacology and Experimental Therapeutics