Quantitative autoradiography of multiple 5-HT1, receptor subtypes in the brain of control or 5,7-dihydroxytryptamine-treated rats

Abstract

The distribution of the 2 main types (A andB) of 5-HT1 binding sites in the rat brain was studied by light-microscopic quantitative autoradiography. The 5-HT1(A) sites were identified using 3H-8-hydroxy-2-(N-dipropylamino)tetralin (3H-8-OH-DPAT) or 3H-5-HT as the ligand. In the latter case. it was shown that 3H-5-HT binding to 5-HT1(A) sites corresponded to that displaceable by 0.1 μM 8-OH-DPAT or 1 μM spiperone. The 'non-5-HT1(A)' sites labeled by 3H-5-HT in the presence of 0.1 μM 8-OH-DPAT corresponded mainly to 5-HT1(B) sites. 5-HT1(A) binding was notably high in limbic regions (dentate gyrus, CA1 and CA3 hippocampal regions, lateral septum, frontal cortex), whereas 5-HT1(B) binding was particularly concentrated in extrapyramidal areas (caudate nucleus, globus pallidus, substantia nigra). Except in the latter regions, where only one class of 5-HT1 sites was found, both 5-HT1(A) and 5-HT1(B) sites existed in all areas examined. The selective degeneration of serotoninergic neurons produced by an intracerebral injection of 5,7-dihydroxytryptamine was associated only with a significant loss of 5-HT1(A) binding to the dorsal raphe nucleus (-60%) and of 5-HT1(B) binding to the substantia nigra (-37%). These results are discussed in relation to the possible identity of 5-HT1(A) and/or 5-HT1(B) sites with the presynaptic 5-HT autoreceptors controlling nerve impulse flow and neurotransmitter release in serotoninergic neurons.