Nervous system distribution of the serotonin 5-HT3 receptor mRNA.

Abstract

The serotonin 5-HT3 receptor subtype has been implicated in many brain functions. Antagonists of this receptor have anxiolytic and antiemetic effects in humans and in animal models. To determine with cellular resolution the distribution of 5-HT3 receptor mRNA, in situ hybridization was performed in sections of mouse brain and dorsal root ganglia. Scattered labeled cells were observed throughout cortical regions, with highest densities in the piriform, cingulate, and entorhinal areas. Strong hybridization signals were seen in the hippocampal formation, where expression appeared primarily in interneurons. Labeled cells were most abundant in the posteroventral hippocampal region, particularly in the lacunosum moleculare layer of CAL. This distribution suggests that 5-HT3 receptors may mediate the known serotonergic inhibition of pyramidal cell populations via excitation of inhibitory interneurons. Labeled cells were also observed in the major subdivisions of the amygdaloid complex, the olfactory bulb, the trochlear nerve nucleus, the dorsal tegmental region, the facial nerve nucleus, the nucleus of the spinal tract of the trigeminal nerve, and the spinal cord dorsal horn. In the periphery, intense hybridization signals were seen in a subpopulation of cells in dorsal root ganglia. The data correlate generally with physiological, behavioral, and receptor autoradiographic studies, provide cellular resolution, and reveal regions of receptor expression not previously observed. The distribution of 5-HT3 receptor mRNA is consistent with roles for the receptor in cognition and affect and in the modulation of sensory input.The monoamine serotonin (5-hydroxytryptamine) has been implicated in a variety of central and peripheral nervous system processes. Its diverse effects are mediated by subclasses of serotonin receptors that were initially defined on the basis of distinct ligand binding profiles (1). Biochemical and molecular genetic characterization of these receptors demonstrates that the 5-HT1, 5-HT2, and 5-HT4 receptor subclasses belong to the superfamily of guanine nucleotide binding protein-coupled receptors (2, 3). In contrast, serotonin 5-HT3 receptors are ligand-gated ion channels that mediate fast excitatory responses (4-6).Responses mediated by 5-HT3 receptors have been characterized in the peripheral nervous system, suggesting roles for the receptor in nociception and gut motility (7)(8)(9)(10). Recently, 5-HT3 receptors have been observed in the brain and have been implicated in many central nervous system processes (11, 12). High levels of 5-HT3 radioligand binding have been detected in the area postrema and solitary tract nucleus (13,14). The antiemetic effects of 5-HT3 antagonists may be attributed to actions at these sites (15,16). Receptor autoradiographic studies have also demonstrated localization of 5-HT3 receptors to cortical and limbic system regions (14,17,18). 5-HT3 receptor antagonists have anxiolytic effects in humans and in animal models (12, 19), perhaps through action at these sites. Re...

Changes in anxiety-related behaviors and hypothalamic–pituitary–adrenal activity in mice lacking the 5-HT-3A receptor

“…Since as there are no reports of the 5-HT-3A receptor being localized in the PVN, AVP mRNA in the PVN may be regulated by afferents to the PVN that contain the 5-HT-3A receptor. The PVN receives strong afferent input from brainstem regions such as the parabrachial nuclei and nucleus tractus solitarius, in which the 5-HT-3 receptor has been localized [6,8]. Whether CRH in the central amygdala can regulate AVP in the PVN is not known.…”

“…Since as there are no reports of 5-HT-3 receptor localization in the central nucleus of the amygdala (see Refs. [5][6][7][8]), the elevated CRH population in the central nucleus of the amygdala in mice lacking the 5-HT-3A receptor is likely secondary to alterations in some other structure and/or peptide such as cholecystokinin, a peptide known to be involved in anxiety [51,52].…”

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

“…Agonist binding at this receptor results in an inward flux of cations and thus an excitation of the host cell (Yakel and Jackson, 1988). 5-HT3 receptors are thought to be most highly expressed in brainstem (Kilpatrick et al, 1989;Gehlert et al, 1991;Laporte et al, 1992;Parker et al, 1996) but have also been detected in dopaminergic brain regions such as the NA (Kilpatrick et al, 1987;Barnes et al, 1990;Gehlert et al, 1991;Parker et al, 1996;Morales et al, 1998), the PFC (Kilpatrick et al, 1987(Kilpatrick et al, , 1989Barnes et al, 1990;Gehlert et al, 1991;Tecott et al, 1993;Morales et al, 1998), the striatum (Kilpatrick et al, 1987(Kilpatrick et al, ,1989Laporte et al, 1992;Parker et al, 1996;Morales et al, 1998) and the SN (Laporte et al, 1992). It is worth noting that the expression of 5-HT3 receptors in the striatum is low in comparison with the PFC and NA.…”

Modulation of Intrinsic Circuits by Serotonin 5-HT3Receptors in Developing Ferret Visual Cortex

“…Our results indicate that a similar mechanism might operate in the neocortex. The expression of 5-HT 3 receptors in neocortical neurons, especially in subpopulations of GABAergic interneurons, has been demonstrated (Tecott et al, 1993;Morales and Bloom, 1997). …”