REGIONAL DIFFERENCES IN THE EFFECTS OF CHRONIC ETHANOL ADMINISTRATIONON [H-3] ZOLPIDEM FINDING IN RAT-BRAIN

A strong association has been observed between [H-3]zolpidem binding a nd the presence of gamma-aminobutyric acid (GABA(A)) receptor mRNA for alpha(1)-, beta(2)-, and gamma(2)-subunits in specific brain regions. This correlates with observed sensitivity of individual neurons to zo lpidem and ethanol in these same regions. Previous studies using homog enate binding approaches showed small alterations in [H-3]zolpidem bin ding levels after chronic ethanol exposure. This study was undertaken to ascertain if there is regional specificity of the effects of chroni c ethanol administration on [H-3]zolpidem binding levels. Chronic etha nol administration induced small, but significant alterations in [H-3] zolpidem (5 nM) binding in the inferior colliculus, substantia nigra, and the medial septum. [H-3]Zolpidem binding was increased in the infe rior colliculus and substantia nigra, and decreased in the medial sept um. No significant differences in [H-3]zolpidem binding were noted in any other brain area analyzed, including the cortex and cerebellum. Th ese findings show that chronic ethanol administration has small effect s on [H-3]zolpidem binding, although they occur in a site-specific and bidirectional manner. Moreover, there is no correlation between chang es in [H-3]zolpidem binding and alterations in GABA(A) receptor subuni t expression.