The effect of chronic (19-day) treatment with the benzodiazepine tranquilizers diazepam (1 mg/kg/day, i.p.) and medazepam (5 mg/kg/day, i.p.) on the binding characteristics of muscarinic receptors in four rat brain structures: cerebral cortex, striatum, hippocampus and hypothalamus were studied using [3H]l-quinuclidinyl benzylate ([3H]QNB) as radioligand. 2. Diazepam and medazepam treatment caused an overall decrease in muscarinic receptor binding affinity (Kd). 3. The number (Bmax) of muscarinic receptors declined in the hippocampus and striatum and rose in the hypothalamus after both benzodiazepines. The Bmax of muscarinic receptors in the cerebral cortex was increased after diazepam treatment. 4. The changes in the binding characteristics of muscarinic receptors might be due to benzodiazepine-induced occurrence of two populations of muscarinic binding sites: P1 (high affinity, low capacity) and P2 (low affinity, high capacity). 5. The altered brain muscarinic receptor functions after chronic diazepam- or medazepam treatment suggest the role of cholinergic neurotransmission in the mechanism of action of benzodiazepines.
