Localization of 5-HT3 receptors in the rat brain using [3H]LY278584

Gehlert, Donald R.; Gackenheimer, Susan L.; Wong, David T.; Robertson, David W.

doi:10.1016/0006-8993(91)90242-n

Cited by 116 publications

(67 citation statements)

References 13 publications

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“…In CA3, a more diffuse plexus of serotonergic terminals exists, predominantly within the stratum oriens and radiatum. This distribution of labeled cells is generally consistent with the distribution of 5-HT3 radioligand binding (18,20).…”

supporting

confidence: 79%

“…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.…”

mentioning

confidence: 99%

“…Infrequently, labeled cells within the pyramidal cell layer were observed. 5-HT3 receptor autoradiographic studies have revealed binding in both the pyramidal cell layer and Lmol in CA1 (18,20). The mismatch in pyramidal cell layer 5-HT3 receptor binding and hybridization could result from the presence of presynaptic 5-HT3 receptors on terminals from neurons located in other layers.…”

mentioning

confidence: 99%

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

Tecott

Maricq

Julius

1993

Proc. Natl. Acad. Sci. U.S.A.

321

177

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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...

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supporting

confidence: 79%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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

Tecott

Maricq

Julius

1993

Proc. Natl. Acad. Sci. U.S.A.

321

177

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“…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.…”

Section: -Ht3 Localizationmentioning

confidence: 99%

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Alex

Pehek

2007

Pharmacology & Therapeutics

525

311

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The neurotransmitter dopamine (DA) has a long association with normal functions such as motor control, cognition, and reward, as well as a number of syndromes including drug abuse, schizophrenia, and Parkinson's disease. Studies show that serotonin (5-HT) acts through several 5-HT receptors in the brain to modulate DA neurons in all three major dopaminergic pathways. There are at least 14 5-HT receptor subtypes, many of which have been shown to play some role in mediating 5-HT/DA interactions. Several subtypes, including the 5-HT1A, 5-HT1B, 5-HT2A, 5-HT3 and 5-HT4 receptors, act to facilitate DA release, while the 5-HT2C receptor mediates an inhibitory effect of 5-HT on DA release. Most 5-HT receptor subtypes only modulate DA release when 5-HT and/or DA neurons are stimulated, but the 5-HT2C receptor, characterized by high levels of constitutive activity, inhibits tonic as well as evoked DA release. This review summarizes the anatomical evidence for the presence of each 5-HT receptor subtype in dopaminergic regions of the brain and the neuropharmacological evidence demonstrating regulation of each DA pathway. The relevance of 5-HT receptor modulation of DA systems to the development of therapeutics used to treat schizophrenia, depression, and drug abuse is discussed. Lastly, areas are highlighted in which future research would be maximally beneficial to the treatment of these disorders.

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“…Using various radioligands, some authors have reported the presence of 5-HT 3 receptors in the striatum of different mammals, albeit higher receptor densities have been found in the human caudate nucleus and putamen than in the corresponding structures of the rat brain (Barnes et al, 1990;Gehlert et al, 1991;Laporte et al, 1992;Abi-Dargham et al, 1993;Bufton et al, 1993;Parker et al, 1996;Morales et al, 1998;Fletcher and Barnes, 1999;Marazziti et al, 2001). Binding studies on homogenates of human putamen suggested a localization of these receptors on neurons that have their cell bodies within this region, such as GABAergic projection neurons, but not on DAergic neurons.…”

Section: Striatummentioning

confidence: 99%

Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders

Matteo

Pierucci

Esposito

et al. 2008

Progress in Brain Research

132

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Several recent studies have emphasized a crucial role for the interactions between serotonergic and dopaminergic systems in movement control and the pathophysiology of basal ganglia. These observations are supported by anatomical evidence demonstrating large serotonergic innervation of all the basal ganglia nuclei. In fact, serotonergic terminals have been reported to make synaptic contacts with both substantia nigra dopamine-containing neurons and their terminal areas such as the striatum, the globus pallidus and the subthalamus. These brain areas contain a high concentration of serotonin (5-HT), with the substantia nigra pars reticulata receiving the greatest input. In this chapter, the distribution of different 5-HT receptor subtypes in the basal ganglia nuclei will be described. Furthermore, evidence demonstrating the serotonergic control of basal ganglia activity will be reviewed and the contribution of the different 5-HT receptor subtypes examined. The new avenues that the increasing knowledge of 5-HT in motor control has opened for exploring the pathophysiology and pharmacology of Parkinson's disease and other movement disorders will be discussed. It is clear that these avenues will be fruitful, despite the disappointing results so far obtained by clinical studies with selective 5-HT ligands. Nevertheless, these studies have led to a great increase in the attention given to the neurotransmitters of the basal ganglia and their connections.

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Localization of 5-HT3 receptors in the rat brain using [3H]LY278584

Cited by 116 publications

References 13 publications

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

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

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders

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