RNA Editing of Serotonin 2C Receptor and Alcohol Intake.

Masaki Tanaka,Yoshihisa Watanabe

doi:10.3389/fnins.2019.01390

Masaki Tanaka, Yoshihisa Watanabe

Open Access

https://doi.org/10.3389/fnins.2019.01390

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Abstract

Serotonin 2C receptor (5-HT2CR) belongs to the superfamily of seven transmembrane domain receptors coupled to G proteins (GPCR). It is broadly distributed in the CNS and its expression is relatively high in the limbic system including the amygdala, nucleus accumbens (NAc), hippocampus, and hypothalamus. Based on its expression patterns and numerous pharmacological studies, 5-HT2CR is thought to be involved in various brain functions including emotion, appetite, and motor behavior. Here, we review 5-HT2CR and its relationship with alcohol intake with a particular focus on the involvement of 5-HT2CR mRNA editing and its association with alcohol preference in mice. RNA editing is a post-transcriptional modification mechanism. In mammals, adenosine is converted to inosine by the deamination enzymes ADAR1 and ADAR2. 5-HT2CR is the only GPCR subjected to RNA editing within the coding region. It has five editing sites in exon 5 that encode the second intracellular loop. Consequently, three amino acids residues (I156, N158, and I160) of the unedited receptor (INI) may be altered to differently edited isoforms, resulting in a change of receptor activity such as 5-HT potency and G-protein coupling. 5-HT2CR in the NAc is involved in enhanced alcohol drinking after chronic alcohol exposure and alterations in 5-HT2CR mRNA editing is important in determining the alcohol preference using different strains of mice and genetically modified mice. RNA editing of this receptor may participate in the development of alcoholism.

Highlights

The serotonin 2C receptor (5-HT2CR) is a member of the 5-HT receptor family, which is divided into seven groups from 5-HT1R to 5-HT7R (Hoyer et al, 1994). 5-HT is produced in neurons located in specific areas of the brainstem that project axons throughout the central nervous system (CNS) (Dahlstroem and Fuxe, 1964). 5-HT acts as a neurotransmitter via receptors and it is involved in the regulation of emotional control, sleep, appetite, and learning
We previously reported that among 5-HT receptors, 5-HT2CR in the nucleus accumbens (NAc) was involved in increased alcohol drinking behavior of C57BL/6J mice after chronic alcohol exposure (Yoshimoto et al, 2012)
C57BL/6J mice showed enhanced alcohol intake after chronic alcohol exposure related to the increased RNA editing of 5-HT2CR; this was not observed in C3H/HeJ or DBA/2J mice that did not show enhanced alcohol intake

Summary

Introduction

The serotonin 2C receptor (5-HT2CR) is a member of the 5-HT receptor family, which is divided into seven groups from 5-HT1R to 5-HT7R (Hoyer et al, 1994). 5-HT is produced in neurons located in specific areas of the brainstem that project axons throughout the central nervous system (CNS) (Dahlstroem and Fuxe, 1964). 5-HT acts as a neurotransmitter via receptors and it is involved in the regulation of emotional control, sleep, appetite, and learning. This is not simple because 5-HT2CR has constitutive activity in the absence of ligand binding and amino acid changes occur due to mRNA editing and alternative splicing. We previously reported that among 5-HT receptors, 5-HT2CR in the NAc was involved in increased alcohol drinking behavior of C57BL/6J mice after chronic alcohol exposure (Yoshimoto et al, 2012).

Results

Conclusion