Chronic phenobarbital administration affects GABA and benzodiazepine receptors in the brain and periphery.

Chronic phenobarbital administration for 20 days to mice resulted in significant increases in the density of peripheral benzodiazepine binding sites in the heart, kidney and cerebellum, but did not affect the density of these sites in the olfactory bulb. No alteration in the affinity (KD) of peripheral benzodiazepine binding sites for their ligand [3H]PK 11195 was observed in any of the organs examined. Phenobarbital treatment did not affect the maximal binding capacity or the affinity of the central benzodiazepine receptors for [3H]flunitrazepam in the cerebral cortex, hippocampus and olfactory bulb. A significant reduction in [3H]muscimol binding in the hippocampus was obtained following chronic phenobarbital treatment. Such an alteration was not detected in the cerebral cortex. The KD values remained unaltered in both tissues. The modulatory effect of phenobarbital on peripheral benzodiazepine binding sites could be related to alterations in the functions of these organs or to the neurochemical effects of the drug.