Differential effects of selective lesions of cholinergic and dopamingergic neurons on serotonin‐type 1 receptors in rat brain

Abstract

Serotonin (5‐HT)‐type₁ (abbreviated as a subscript 1) receptor binding sites are discretely distributed in rat brain. High densities of [³H]5‐HT₁ binding sites are especially located in areas enriched with cholinergic and dopaminergic innervation, such as the substantia innominata/ventral pallidum, striatum, septal nuclei, hippocampus and substantia nigra. The possible association of [³H]5‐HT₁ binding sites with cholinergic or dopminergic cell bodies and/or nerve fiber terminals was investigated by selective lesions of the substantia innominata/ventral pallidum‐cortical and septohippocampal cholinergic pathways and the nigrostriatal dopaminergic projection. [³H]5‐HT₁ receptor binding sites are possibly located on cholinergic cell bodies in the ventral pallidum‐cortical pathway since [³H]5‐HT₁ binding in the substantia innominata/ventral pallidal area was markedly decreased following kainic acid lesions. Fimbriaectomies markedly decreased [³H]5‐HT₁ binding in the hippocampus, suggesting the presence of 5‐HT₁ binding sites on cholinergic nerve fiber terminals in the septohippocampal pathway. Lesions of the nigrostriatal dopaminergic projection did not modify [³H]5‐HT₁ binding in the substantia nigra and the striatum, suggesting that 5‐HT₁ receptors are not closely associated with dopaminergic cell bodies and nerve terminals in this pathway. These results demonstrate differential association between 5‐HT₁ receptors and cholinergic and dopaminergic innervation in rat brain.