Clonazepam-induced up-regulation of serotonin1 and serotonin2 binding sites in rat frontal cortex.

Chronic administration of the benzodiazepine clonazepam increased the number of [3H]5-HT (5-HT1) and [3H]SPIP (5-HT2) binding sites in rat frontal cortex. In each instance, binding changes reflected increases in the maximum densities of binding sites (Bmax) with no change in ligand affinities (KD). Increases in binding required continued clonazepam exposure (10 days) at high doses. [3H]5-HT binding was significantly elevated at daily dose levels (i.p.) of 5.0 mg/kg but not 2.5 mg/kg. [3H]SPIP binding was significantly increased at drug doses of 2.5 mg/kg but not 1.0 mg/kg. Binding changes were regional in that they occurred in membranes from frontal cortex but not brainstem. A second benzodiazepine, diazepam, did not affect either binding site at daily doses of 30 mg/kg. These data suggest that serotonin receptor changes seen after chronic clonazepam may occur as a compensatory response to decreases in the presynaptic release of serotonin.