Chronic Effects of Imipramine and Lithium on 5-HT Receptor Subtypes in Rat Frontal Cortex, Hippocampus and Choroid Plexus: Quantitative Receptor Autoradiographic Analysis

Abstract

The effects of chronic treatment with imipramine or lithium on serotonin (5-HT) receptor subtypes were analyzed in the frontal cortex, hippocampus and choroid plexus of rat brain by quantitative receptor autoradiographic procedures, using radioligands [³H]-5-HT, [³H]-8-hydroxy-2-(di-n-propylamino)tetralin ([³H]-8-OH-DPAT), [¹²⁵I]-iodocyanopindolol ([¹²⁵I]-CYP), [³H]-mesulergine and [¹²⁵I]-7-amino-8-iodo-ketanserin ([¹²⁵I]-ketanserin) or [³H]-spiperone. Chronic i.p. administration of imipramine (20 mg/kg/day for 21 days) decreased the densities of 5-HT₁, 5-HT_1A, 5-HT_1C, and 5-HT₂ sites in the frontal cortex, hippocampus and choroid plexus. Lithium (2 mEq/kg/day for 21 days) also decreased the densities of 5-HT₁, 5-HT_1C, and 5-HT₂ sites in the frontal cortex, and the densities of those including 5-HT_1A sites in the hippocampus and choroid plexus. Imipramine and lithium very markedly decreased the density of 5-HT_1C, sites in the choroid plexus. We propose that methods employing quantitative receptor autoradiographic analysis can be used to characterize and understand the local effects of these drugs on 5-HT receptor subtypes.