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 and B) of 5-HT1 binding sites in the rat brain was studied by light-microscopic quantitative autoradiography. The 5-HT1A 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-HT1A sites corresponded to that displaceable by 0.1 microM 8-OH-DPAT or 1 microM spiperone. The "non-5-HT1A" sites labeled by 3H-5-HT in the presence of 0.1 microM 8-OH-DPAT corresponded mainly to 5-HT1B sites. 5-HT1A binding was notably high in limbic regions (dentate gyrus, CA1 and CA3 hippocampal regions, lateral septum, frontal cortex), whereas 5-HT1B 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-HT1A and 5-HT1B 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-HT1A binding to the dorsal raphe nucleus (-60%) and of 5-HT1B binding to the substantia nigra (-37%). These results are discussed in relation to the possible identity of 5-HT1A and/or 5-HT1B sites with the presynaptic 5-HT autoreceptors controlling nerve impulse flow and neurotransmitter release in serotoninergic neurons.

Distinguishing characteristics of serotonin and non-serotonin-containing cells in the dorsal raphe nucleus: electrophysiological and immunohistochemical studies

“…7 shows fluorescent photomicrographs depicting 5-HT-IR (green) and 5-HT 1A receptor-IR cells (red) in the ventromedial subdivision of the DRN (left panels: low magnification and right panels: high magnification). Consistent with several reports (Weissmann-Nanopoulos et al, 1985;Verge et al, 1986;Sotelo et al, 1990;Miquel et al, 1992), the majority of 5-HT-containing cells also expressed 5-HT 1A receptors. Nonetheless, a significant number of single labeled neurons that were 5-HT 1A -IR were observed and these were interdigitated with 5-HT-IR neurons.…”

“…Consistent with these findings, a recent study in our laboratory demonstrated that though lesions of the 5-HT system with 5,7-DHT significantly reduce 5-HT 1A receptor binding in the DRN, a substantial number of binding sites remain (42%) (Kirby et al, 2001). Previous serotonergic lesion studies have shown spared 5-HT 1A receptor binding sites or receptor mRNA to range from 10 to 40% (Weissmann-Nanopoulos et al, 1985;Verge et al, 1986;Miquel et al, 1992). It is likely that at least a subset of these spared neurons remain because of their localization on non-5-HT neurons.…”

“…The anatomical data presented in this study are consistent with these findings. Previous studies have used selective 5-HT lesions with 5,7-DHT (Weissmann- Nanopoulos et al, 1985;Verge et al, 1986;Miquel et al, 1992) and more direct immunohistochemical evidence using 5-HT-IR and 5-HT 1A receptor-IR labeling in adjacent sections (Sotelo et al, 1990) to argue for the presence of 5-HT 1A receptors on 5-HT DRN neurons. As expected, we found that the majority of 5-HT-IR+ neurons in the DRN were double-labeled for 5-HT 1A receptor-IR.…”

Serotonin Function in Panic Disorder: Important, But Why?

“…It is conceivable that these changes reflect a deficit in 5-HT neurotransmission or a compensatory process in the 5-HT system that attempts to increase the availability of synaptic 5-HT. The downregulation of postsynaptic 5-HT1A receptors, however, is not likely to reflect an adaptive response to abnormal 5-HT release because reducing 5-HT transmission by lesioning the raphe or administering 5-HT synthesis inhibitors does not alter 5-HT1A receptor binding in the cerebral cortex or the hippocampus (Frazer and Hensler, 1990;Hensler et al, 1991;Pranzatelli et al, 1994;Verge et al, 1986). Also, an increased 5-HT transmission after treatment with an SSRI or MAOI does not consistently alter 5-HT1A receptor density or mRNA concentrations in the cortex, hippocampus, or amygdala (Carli et al, 1996;Hensler et al, 1991;Spurlock et al, 1994;Welner et al, 1989).…”

Effect of Chronic Serotonin-2 Receptor Agonist or Antagonist Administration on Serotonin-1A Receptor Sensitivity

“…The unique distribution of this serotonin receptor subtype in brain is consistent with its potential involvement in cognitive or integrative functions, as well as in emotional states. In terminal field areas of serotonergic innervation, the 5-HT 1A receptor is located postsynaptically and is present in high density in cortical and limbic structures (i.e., hippocampus, entorhinal cortex, septum, amygdala, frontal cortex) (Vergé et al 1986;Hensler et al 1991;Khawaja 1995). The 5-HT 1A receptor is also found in high density in serotonin cell body areas, such as the dorsal and median raphé, where it is believed to function as the somatodendritic autoreceptor modulating the activity of serotonergic neurons (see Aghajanian et al 1990).…”