Benzodiazepine response and receptor binding after chronic ethanol ingestion in a mouse model.
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.
Barnhill
J G
JG
Department of Psychiatry, Tufts-New England Medical Center, Boston, Massachusetts.
Ciraulo
D A
DA
Greenblatt
D J
DJ
Faggart
M A
MA
Harmatz
J S
JS
D000437:Alcoholism / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism; D002998:Clonazepam / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism* / Q000502:physiology
D011963:Receptors, GABA-A; D001569:Benzodiazepines; D000431:Ethanol; D002998:Clonazepam