Specific effects of chronic phenobarbital administration on high- and low-affinity benzodiazepine receptors in mouse cerebellum and forebrain.

Characteristics of [3H]flunitrazepam ([3H]FLU) binding to cortical and cerebellar membrane receptors were examined following chronic (six days) administration of phenobarbital (PB) to C57B1 mice. Following PB treatment, the number of [3H]FLU binding sites (Bmax) was significantly reduced in both cerebral cortex and in cerebellum. No change in the affinity (KD) of these binding sites was observed. Using 3-methyl-6-[3-(trifluoromethyl)phenyl]-1,2,4-triazolo [4,3-beta]pyridazine (CL-218,872), further analysis revealed a significant decrease in the number of high-affinity CL-218,872 binding sites in cerebellar tissue. In the forebrain areas, however, a significant decrease in the number of low-affinity binding sites was found. Finally, the enhancement of [3H]FLU binding, produced by in vitro addition of pentobarbital, was significantly less pronounced in the cerebellum of PB-treated animals.