Chronic ethanol exposure increases peripheral-type benzodiazepine receptors in brain.
The effect of chronic ethanol exposure, withdrawal from chronic exposure and short-term ethanol exposure on mouse brain peripheral-type benzodiazepine receptors (PBR) and on PBR from selected peripheral tissues was studied. Male C57BL/6J mice were fed an ethanol-containing liquid diet for 7.75 or 9 days under conditions which produced physical dependence. Control mice received the diet with isocaloric carbohydrates substituted for ethanol. The binding of [3H]Ro5-4864 to PBR was increased in brain membranes, but not heart or kidney membranes, of mice exposed to ethanol for 7.75 days. Scatchard plot analysis indicated that the increase was due to an increase in the apparent number of binding sites and not to a change in receptor affinity. The same results were obtained in ethanol-dependent mice that were withdrawn from the ethanol for 12 h prior to binding determinations. The binding of [3H]PK-11195 to brain PBR was likewise increased in mice made physically dependent on ethanol after 9 days exposure. In contrast to the effects of chronic exposure using the liquid diet, repeated short-term exposure to ethanol following a procedure known to cause functional tolerance (3.6 g/kg i.p. once daily for 4 days) did not significantly affect the binding of [3H]Ro5-4864 to brain when compared to saline-injected and naive control mice. The results are consistent with previous findings and suggest that ethanol exposure causes time-dependent changes in brain PBR that may be linked to the development of physical dependence. However, further studies are necessary to determine whether the increase in brain PBR sites of alcohol-dependent mice is causally related to the development of alcohol dependence.
Syapin
P J
PJ
Department of Psychiatry, School of Medicine, University of Southern California, Los Angeles 90033.
Alkana
R L
RL
D000818:Animals; D001570:Benzodiazepinones / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003292:Convulsants / Q000378:metabolism; D004032:Diet; D000431:Ethanol / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011963:Receptors, GABA-A / Q000187:drug effects*; D019966:Substance-Related Disorders / Q000503:physiopathology
D001570:Benzodiazepinones; D003292:Convulsants; D007546:Isoquinolines; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D000431:Ethanol; C037850:PK 11195