Down-Regulation of Benzodiazepine Binding to a5 Subunit- Containing g-Aminobutyric AcidA Receptors in Tolerant Rat Brain Indicates Particular Involvement of the Hippocampal CA1

Chronic benzodiazepine treatment can produce tolerance and changes in g-aminobutyric acid (GABA)A receptors. To study the effect of treatment on a selected population of receptors, assays were performed using [3H]RY-80, which is selective for GABAA receptors with an a5 subunit. Rats were given a fluraz-epam treatment known to produce tolerance and down-regu-lation of benzodiazepine binding, or a diazepam treatment shown to produce tolerance but not receptor down-regulation. Quantitative receptor autoradiography using sagittal brain sec-tions bound with [3H]RY-80 showed binding in areas known to express a5 mRNA. Brains from flurazepam-treated rats showed significantly decreased 1 nM [3H]RY-80 binding in hippocampal formation (e.g., 32 % decrease in CA1) and superior colliculus, but not other areas. Using 5 nM [3H]RY-80 showed simila