• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Feb 15, 1993; 90(4): 1430–1434.

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


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 CA1. 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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.8M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Peroutka SJ, Snyder SH. Multiple serotonin receptors: differential binding of [3H]5-hydroxytryptamine, [3H]lysergic acid diethylamide and [3H]spiroperidol. Mol Pharmacol. 1979 Nov;16(3):687–699. [PubMed]
  • Hartig PR. Molecular biology of 5-HT receptors. Trends Pharmacol Sci. 1989 Feb;10(2):64–69. [PubMed]
  • Julius D. Molecular biology of serotonin receptors. Annu Rev Neurosci. 1991;14:335–360. [PubMed]
  • Yakel JL, Jackson MB. 5-HT3 receptors mediate rapid responses in cultured hippocampus and a clonal cell line. Neuron. 1988 Sep;1(7):615–621. [PubMed]
  • Derkach V, Surprenant A, North RA. 5-HT3 receptors are membrane ion channels. Nature. 1989 Jun 29;339(6227):706–709. [PubMed]
  • Maricq AV, Peterson AS, Brake AJ, Myers RM, Julius D. Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel. Science. 1991 Oct 18;254(5030):432–437. [PubMed]
  • Richardson BP, Engel G, Donatsch P, Stadler PA. Identification of serotonin M-receptor subtypes and their specific blockade by a new class of drugs. Nature. 1985 Jul 11;316(6024):126–131. [PubMed]
  • GADDUM JH, PICARELLI ZP. Two kinds of tryptamine receptor. Br J Pharmacol Chemother. 1957 Sep;12(3):323–328. [PMC free article] [PubMed]
  • Gordon JC, Barefoot DS, Sarbin NS, Pinkus LM. [3H]zacopride binding to 5-hydroxytryptamine3 sites on partially purified rabbit enteric neuronal membranes. J Pharmacol Exp Ther. 1989 Dec;251(3):962–968. [PubMed]
  • Kilpatrick GJ, Jones BJ, Tyers MB. Identification and distribution of 5-HT3 receptors in rat brain using radioligand binding. Nature. 1987 Dec 24;330(6150):746–748. [PubMed]
  • Costall B, Naylor RJ, Tyers MB. The psychopharmacology of 5-HT3 receptors. Pharmacol Ther. 1990;47(2):181–202. [PubMed]
  • Waeber C, Dixon K, Hoyer D, Palacios JM. Localisation by autoradiography of neuronal 5-HT3 receptors in the mouse CNS. Eur J Pharmacol. 1988 Jul 7;151(2):351–352. [PubMed]
  • Kilpatrick GJ, Jones BJ, Tyers MB. The distribution of specific binding of the 5-HT3 receptor ligand [3H]GR65630 in rat brain using quantitative autoradiography. Neurosci Lett. 1988 Nov 22;94(1-2):156–160. [PubMed]
  • Costall B, Domeney AM, Naylor RJ, Tattersall FD. 5-Hydroxytryptamine M-receptor antagonism to prevent cisplatin-induced emesis. Neuropharmacology. 1986 Aug;25(8):959–961. [PubMed]
  • Waeber C, Pinkus LM, Palacios JM. The (S)-isomer of [3H]zacopride labels 5-HT3 receptors with high affinity in rat brain. Eur J Pharmacol. 1990 Jun 8;181(3):283–287. [PubMed]
  • Gehlert DR, Gackenheimer SL, Wong DT, Robertson DW. Localization of 5-HT3 receptors in the rat brain using [3H]LY278584. Brain Res. 1991 Jul 5;553(1):149–154. [PubMed]
  • Barnes JM, Barnes NM, Cooper SJ. Behavioural pharmacology of 5-HT3 receptor ligands. Neurosci Biobehav Rev. 1992 Spring;16(1):107–113. [PubMed]
  • Oleskevich S, Descarries L. Quantified distribution of the serotonin innervation in adult rat hippocampus. Neuroscience. 1990;34(1):19–33. [PubMed]
  • Lacaille JC, Schwartzkroin PA. Stratum lacunosum-moleculare interneurons of hippocampal CA1 region. I. Intracellular response characteristics, synaptic responses, and morphology. J Neurosci. 1988 Apr;8(4):1400–1410. [PubMed]
  • Freund TF, Gulyás AI, Acsády L, Görcs T, Tóth K. Serotonergic control of the hippocampus via local inhibitory interneurons. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8501–8505. [PMC free article] [PubMed]
  • Ropert N, Guy N. Serotonin facilitates GABAergic transmission in the CA1 region of rat hippocampus in vitro. J Physiol. 1991 Sep;441:121–136. [PMC free article] [PubMed]
  • Lacaille JC, Schwartzkroin PA. Stratum lacunosum-moleculare interneurons of hippocampal CA1 region. II. Intrasomatic and intradendritic recordings of local circuit synaptic interactions. J Neurosci. 1988 Apr;8(4):1411–1424. [PubMed]
  • Assaf SY, Miller JJ. The role of a raphe serotonin system in the control of septal unit activity and hippocampal desynchronization. Neuroscience. 1978;3(6):539–550. [PubMed]
  • Vanderwolf CH. A general role for serotonin in the control of behavior: studies with intracerebral 5,7-dihydroxytryptamine. Brain Res. 1989 Dec 18;504(2):192–198. [PubMed]
  • Nilsson OG, Strecker RE, Daszuta A, Björklund A. Combined cholinergic and serotonergic denervation of the forebrain produces severe deficits in a spatial learning task in the rat. Brain Res. 1988 Jun 21;453(1-2):235–246. [PubMed]
  • Richter-Levin G, Segal M. Raphe cells grafted into the hippocampus can ameliorate spatial memory deficits in rats with combined serotonergic/cholinergic deficiencies. Brain Res. 1989 Jan 23;478(1):184–186. [PubMed]
  • Molineaux SM, Jessell TM, Axel R, Julius D. 5-HT1c receptor is a prominent serotonin receptor subtype in the central nervous system. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6793–6797. [PMC free article] [PubMed]
  • Voigt MM, Laurie DJ, Seeburg PH, Bach A. Molecular cloning and characterization of a rat brain cDNA encoding a 5-hydroxytryptamine1B receptor. EMBO J. 1991 Dec;10(13):4017–4023. [PMC free article] [PubMed]
  • Pompeiano M, Palacios JM, Mengod G. Distribution and cellular localization of mRNA coding for 5-HT1A receptor in the rat brain: correlation with receptor binding. J Neurosci. 1992 Feb;12(2):440–453. [PubMed]
  • Sugita S, Shen KZ, North RA. 5-hydroxytryptamine is a fast excitatory transmitter at 5-HT3 receptors in rat amygdala. Neuron. 1992 Jan;8(1):199–203. [PubMed]
  • Costall B, Jones BJ, Kelly ME, Naylor RJ, Onaivi ES, Tyers MB. Sites of action of ondansetron to inhibit withdrawal from drugs of abuse. Pharmacol Biochem Behav. 1990 May;36(1):97–104. [PubMed]
  • Simerly RB, Swanson LW, Gorski RA. Demonstration of a sexual dimorphism in the distribution of serotonin-immunoreactive fibers in the medial preoptic nucleus of the rat. J Comp Neurol. 1984 May 10;225(2):151–166. [PubMed]
  • Hayakawa T, Zyo K. Fine structure of the lateral mammillary projection to the dorsal tegmental nucleus of Gudden in the rat. J Comp Neurol. 1990 Aug 8;298(2):224–236. [PubMed]
  • Sutin EL, Jacobowitz DM. Immunocytochemical localization of peptides and other neurochemicals in the rat laterodorsal tegmental nucleus and adjacent area. J Comp Neurol. 1988 Apr 8;270(2):243–270. [PubMed]
  • Rasmussen K, Aghajanian GK. Serotonin excitation of facial motoneurons: receptor subtype characterization. Synapse. 1990;5(4):324–332. [PubMed]
  • Pratt GD, Bowery NG. The 5-HT3 receptor ligand, [3H]BRL 43694, binds to presynaptic sites in the nucleus tractus solitarius of the rat. Neuropharmacology. 1989 Dec;28(12):1367–1376. [PubMed]
  • Hamon M, Gallissot MC, Menard F, Gozlan H, Bourgoin S, Vergé D. 5-HT3 receptor binding sites are on capsaicin-sensitive fibres in the rat spinal cord. Eur J Pharmacol. 1989 May 19;164(2):315–322. [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links