Premium
Serotonin 2C receptors in the nucleus accumbens are involved in enhanced alcohol‐drinking behavior
Author(s) -
Yoshimoto Kanji,
Watanabe Yoshihisa,
Tanaka Masaki,
Kimura Minoru
Publication year - 2012
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2012.08037.x
Subject(s) - nucleus accumbens , ventral tegmental area , dorsal raphe nucleus , chemistry , medicine , endocrinology , receptor antagonist , receptor , serotonin , dopamine , alcohol , antagonist , biology , biochemistry , serotonergic , dopaminergic
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.