title: Serotonin2C receptors in the nucleus accumbens are involved in enhanced alcohol-drinking behavior.
abstract: Dopamine and serotonin (5-HT) in the nucleus accumbens (ACC) and ventral tegmental area of the mesoaccumbens reward pathways have been implicated in the mechanisms underlying development of alcohol dependence. We used a C57BL/6J mouse model with increased voluntary alcohol-drinking behavior by exposing the mice to alcohol vapor for 20 consecutive days. In the alcohol-exposed mice, the expression of 5-HT(2C)  receptor mRNA increased in the ACC, caudate nucleus and putamen, dorsal raphe nucleus (DRN), hippocampus and lateral hypothalamus, while the protein level of 5-HT(2C)  receptor significantly increased in the ACC. The expression of 5-HT(7)  receptor mRNA increased in the ACC and DRN. Contents of 5-HT decreased in the ACC shell (ACC(S) ) and DRN of the alcohol-exposed mice. The basal extracellular releases of dopamine (DA) and 5-HT in the ACC(S)  increased more in the alcohol-exposed mice than in alcohol-naïve mice. The magnitude of the alcohol-induced ACC(S)  DA and 5-HT release in the alcohol-exposed mice was increased compared with the control mice. Intraperitoneal (i.p.) administration or local injection into ACC(S)  of the 5-HT(2C)  receptor antagonist, SB-242084, suppressed voluntary alcohol-drinking behavior in the alcohol-exposed mice. But the i.p. administration of the 5-HT(7)  receptor antagonist, SB-258719, did not have significant effects on alcohol-drinking behavior in the alcohol-exposed mice. The effects of the 5-HT(2C)  receptor antagonist were not observed in the air-exposed control mice. These results suggest that adaptations of the 5-HT system, especially the upregulation of 5-HT(2C)  receptors in the ACC(S) , are involved in the development of enhanced voluntary alcohol-drinking behavior.
authors.affiliation: Department of Forensic Medicine, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan. kyoshimo@koto.kpu-m.ac.jp
authors.forename: Kanji
authors.initials: K
authors.lastname: Yoshimoto
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Masaki
authors.initials: M
authors.lastname: Tanaka
authors.forename: Minoru
authors.initials: M
authors.lastname: Kimura
mesh_terms: D000428:Alcohol Drinking / Q000473:pathology* / Q000503:physiopathology; D000631:Aminopyridines / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D008845:Microinjections / Q000379:methods; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D000631:Aminopyridines; D015306:Biogenic Monoamines; D002492:Central Nervous System Depressants; D000431:Ethanol; D007211:Indoles; D010880:Piperidines; D012333:RNA, Messenger; D044405:Receptor, Serotonin, 5-HT2C; D011954:Receptors, Dopamine; D018490:Serotonin Agents; D013449:Sulfonamides; C111309:3,N-dimethyl-N-(1-methyl-3-(4-methylpiperidin-1-yl)propyl)benzenesulfonamide; D000096926:Benzenesulfonamides; C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline