Differential effects of selective lesions of cholinergic and dopaminergic neurons on serotonin-type 1 receptors in rat brain.

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 dopaminergic 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.