P-Chlorophenylalanine-reversible reduction of σ binding sites by chronic imipramine treatment in rat brain

Abstract

Repeated treatment with imipramine (10 mg/kg intraperitoneally (i.p.), once daily for 14 days) caused a decrease in the B max, without affecting the K d, of [ 3H]DTG (1,3-di-o-tolylguanidine) binding to the haloperidol-sensitive σ sites in the striatum, hippocampus and cerebral cortex of the rat. A similar reduction was observed after chronic administration of a selective serotonin uptake inhibitor, fluoxetine (10 mg/kg i.p., twice daily for 14 days), but not of a selective norepinephrine uptake inhibitor, desipramine (10 mg/kg i.p., once daily for 14 days). Neither a single injection of imipramine (10 mg/kg i.p.) nor addition of imipramine or fluoxetine into the binding assay medium mimicked the changes in the maximal binding of brain σ sites induced by chronic treatment with these drugs. Finally, depletion of brain serotonin by means of repeated administration of p-chlorophenylalanine, which produces inhibition of the amine synthesis, blocked the ability of repeated imipramine treatment to reduce the maximal number of [ 3H]DTG binding sites in the striatum and hippocampus. The present results suggest that cerebral serotonergic transmission may play a role in the regulation of cerebral σ binding sites in the rat.