Distribution and cellular localization of the serotonin type 2C receptor messenger RNA in human brain
Section snippets
Cloning and sequencing
Total RNA was prepared from human choroid plexus using the guanidine–thiocyanate/acid phenol method11 and poly(A)+ RNA was isolated with paramagnetic beads (oligodT Dynabeads, Dynal, Oslo, Norway).
0.5 mg of poly(A)+ RNA were reverse-transcribed in the presence of random hexamers and 2.5 U of MULV reverse transcriptase (Perkin Elmer-Cetus, Norwalk, CT). The first strand cDNA was used as a substrate for a polymerase chain reaction (PCR) experiment with two specific primers corresponding to
Results
The anatomical distribution of the 5-HT2C mRNA was analysed in histological sections of the cerebral cortex, hippocampus, amygdala, basal ganglia, substantia innominata (basal nucleus of Meynert), ventromedial hypothalamus, substantia nigra, cerebellum and choroid plexus. Some sections of each sample were not processed for in situ hybridization, but were stained with Cresyl Violet in order to permit a detailed analysis of the cytoarchitecture. The identification of the various brain structures
Discussion
Our study represents the first detailed mapping of the cells expressing 5-HT2C receptor mRNA in some regions of the human brain. Our work confirmed previous observations that the highest levels of 5-HT2C mRNA expression were in the choroid plexus epithelium.26., 28. We confirmed also, by means of reverse transcription (RT)–PCR experiments, the presence in the choroid plexus of an alternatively spliced 5-HT2C RNA variant that contains a 95 nt deletion in the region coding for the second
Conclusion
In conclusion, the present results taken together point to a significant role for the 5-HT2C receptor in the functional activity of several brain pathways. A further characterization of the cells expressing 5-HT2C mRNA, by using in situ hybridization combined with immunocytochemistry, could provide valuable information with regard to the functions of the 5-HT2C receptor in the human brain.
Acknowledgements
This work was supported by a grant from the Department of Education (Murst). We thank Dr Sabina Macchi for primers design and synthesis and Dr Yuri Bozzi for helpful discussion.
References (36)
- et al.
Molecular biology of 5-HT receptors
Neuropharmacology
(1994) - et al.
5-HT: on the psychiatrist's couch
Trends pharmac. Sci.
(1992) - et al.
The distribution of 5-HT1A receptor mRNA in human brain
Brain Res.
(1995) - et al.
Binding of typical and atypical antipsychotics in 5-HT1C and 5-HT2 sites: clozapine potently interacts with 5-HT1C sites
Eur. J. Pharmac.
(1990) - et al.
Detection of mRNAs in sea urchin embryos by in situ hybridization using asymmetric RNA probes
Devl Biol.
(1984) - et al.
Anger and anxiety responses to m-chlorophenylpiperazine in generalized anxiety disorder
Biol. Psychiat.
(1992) - et al.
5-HT receptor classification and nomenclature: towards a harmonization with the human genome
Neuropharmacology
(1997) - et al.
Anxiogenic-like effects of mCPP and TFMPP in animal models are opposed by 5-HT1C receptor antagonists
Eur. J. Pharmac.
(1989) - et al.
The distribution and cellular localization of the serotonin 1C receptor mRNA in the rodent brain examined by in situ hybridization histochemistry. Comparison with receptor binding distribution
Neuroscience
(1990) - et al.
Comparative anatomical distribution of serotonin 1A, 1Dα and 2A receptor mRNA in human brain postmortem
Molec. Brain Res.
(1996)
Distribution of the 5-HT5A serotonin receptor mRNA in the human brain
Molec. Brain Res.
The binding of serotoninergic ligands to the porcine choroid plexus: characterization of a new type of serotonin recognition site
Eur. J. Pharmac.
Quantitative autoradiographic mapping of serotonin receptors in the rat brain. I. Serotonin-1 receptors
Brain Res.
Serotonin receptors in the human brain. III. Autoradiographic mapping of serotonin-1 receptors
Neuroscience
A comparison of the behavioral effects of oral versus intravenous m-CPP administration in OCD patients and the effect of metergoline prior to IV m-CPP
Biol. Psychiat.
Distribution of the serotonin 5-HT2 receptor family mRNAs: comparison between 5-HT2A and 5-HT2C receptors
Molec. Brain Res.
Cloning of the human serotonin 5-HT2A and 5-HT1C receptor subtypes
Biochem. biophys. Res. Commun.
The human serotonin 5-HT2C receptor: complete cDNA, genomic structure, and alternatively spliced variant
Genomics
Cited by (136)
A long and winding road: My personal journey to oxytocin with no return
2023, Comprehensive PsychoneuroendocrinologyEffects of low doses of different nitric oxide (NO) donors in rat models of obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD)
2022, Nitric Oxide - Biology and ChemistryCitation Excerpt :These findings propose that the effects of mCPP on grooming behaviour, are mediated, at least, by stimulation of the 5-HT2C receptor [18]. This receptor is expressed in brain areas associated to OCD pathology, such as the basal ganglia and orbitofrontal and cingulate cortices [7,38,41,47]. Based on the above, it can be hypothesized that SNP and molsidomine might attenuate the excessive grooming induced by mCPP by an antagonistic action at the 5-HT2C receptor site.
Serotonin/dopamine interaction: Electrophysiological and neurochemical evidence
2021, Progress in Brain Research5-HT/GABA interaction in epilepsy
2021, Progress in Brain ResearchConstitutive activity of 5-HT receptors: Factual analysis
2020, NeuropharmacologySerotonergic control of excitability: from neuron to networks
2020, Handbook of Behavioral NeuroscienceCitation Excerpt :As far as we know, this clear-cut distinct distribution is less evident for the other 5-HT receptors. 5-HT2C receptors would be mostly somatodendritic but strong arguments suggest that they can be addressed at terminals of some neurons (De Deurwaerdere et al., 2013; Pasqualetti et al., 1999). Examples of both distributions can be found for the other 5-HT receptors including 5-HT4 receptors (Compan et al., 1996; Vilaro et al., 2005), 5-HT6 receptors (Gerard et al., 1996, 1997), and 5-HT7 receptors (Heidmann et al., 1997; To et al., 1995; Varnas et al., 2004).