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Nicotinic alpha 4 Receptor-Mediated Cholinergic Influences on Food Intake and Activity Patterns in Hypothalamic Circuits
Garcia, Ana P.1,2; Aitta-aho, Teemu1; Schaaf, Laura1; Heeley, Nicholas3; Heuschmid, Lena1; Bai, Yunjing1,4; Barrantes, Francisco J.2; Apergis-Schoute, John1,3
2015-08-06
发表期刊PLOS ONE
ISSN1932-6203
文章类型Article
卷号10期号:8页码:1-12
摘要Nicotinic acetylcholine receptors (nAChRs) play an important role in regulating appetite and have been shown to do so by influencing neural activity in the hypothalamus. To shed light on the hypothalamic circuits governing acetylcholine's (ACh) regulation of appetite this study investigated the influence of hypothalamic nAChRs expressing the alpha 4 subunit. We found that antagonizing the alpha 4 beta 2 nAChR locally in the lateral hypothalamus with di-hydro-beta-erythroidine (DH beta E), an alpha 4 nAChR antagonist with moderate affinity, caused an increase in food intake following free access to food after a 12 hour fast, compared to saline-infused animals. Immunocytochemical analysis revealed that orexin/hypocretin (HO), oxytocin, and tyrosine hydroxylase (TH)-containing neurons in the A13 and A12 of the hypothalamus expressed the nAChR alpha 4 subunit in varying amounts (34%, 42%, 50%, and 51%, respectively) whereas melanin concentrating hormone (MCH) neurons did not, suggesting that DH beta E-mediated increases in food intake may be due to a direct activation of specific hypothalamic circuits. Systemic DH beta E (2 mg/kg) administration similarly increased food intake following a 12 hour fast. In these animals a subpopulation of orexin/hypocretin neurons showed elevated activity compared to control animals and MCH neuronal activity was overall lower as measured by expression of the immediate early gene marker for neuronal activity cFos. However, oxytocin neurons in the paraventricular hypothalamus and TH-containing neurons in the A13 and A12 did not show differential activity patterns. These results indicate that various neurochemically distinct hypothalamic populations are under the influence of alpha 4 beta 2 nAChRs and that cholinergic inputs to the lateral hypothalamus can affect satiety signals through activation of local alpha 4 beta 2 nAChR-mediated transmission.
收录类别SCI
语种英语
WOS记录号WOS:000359062300012
引用统计
文献类型期刊论文
条目标识符http://ir.psych.ac.cn/handle/311026/15206
专题中国科学院心理健康重点实验室
作者单位1.Univ Cambridge, Dept Pharmacol, Cambridge CB2 1QJ, England
2.Catholic Univ Argentina, Fac Med Sci, UCA CONICET, Mol Neurobiol Lab,Biomed Res Inst BIOMED, Buenos Aires, DF, Argentina
3.Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Cambridge CB2 1QJ, England
4.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China
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Garcia, Ana P.,Aitta-aho, Teemu,Schaaf, Laura,et al. Nicotinic alpha 4 Receptor-Mediated Cholinergic Influences on Food Intake and Activity Patterns in Hypothalamic Circuits[J]. PLOS ONE,2015,10(8):1-12.
APA Garcia, Ana P..,Aitta-aho, Teemu.,Schaaf, Laura.,Heeley, Nicholas.,Heuschmid, Lena.,...&Apergis-Schoute, John.(2015).Nicotinic alpha 4 Receptor-Mediated Cholinergic Influences on Food Intake and Activity Patterns in Hypothalamic Circuits.PLOS ONE,10(8),1-12.
MLA Garcia, Ana P.,et al."Nicotinic alpha 4 Receptor-Mediated Cholinergic Influences on Food Intake and Activity Patterns in Hypothalamic Circuits".PLOS ONE 10.8(2015):1-12.
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