並列タイトル等母子分離ストレスが報酬探索行動に及ぼす影響と側坐核におけるドーパミンD1受容体のDNAのメチル化機構を介した発現変化について
一般注記type:Thesis
Early-life stress has long-lasting effects on the stress response, emotions, and behavior throughout an individual’s life. Clinical reports have demonstrated that child abuse victims exhibit impairments in reward-associated behavior; yet, the mechanism for this effect remains unclear. Maternal separation (MS) or MS coupled with social isolation (SI) (MS + SI) is widely used as a model for early-life stress in rodent studies. We employed mice subjected to MS + SI to clarify the long-term effect of early-life stress on reward-seeking involving palatable foods by a conditioned place-preference (CPP) paradigm. Prior MS + SI experience decreased exploration time in a chocolate-paired compartment in adult female mice, but not in male mice. We then focused on the mesolimbic dopamine pathway associated with reward-seeking behavior and measured both mRNA and protein levels of tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and dopamine D1 and D2 receptors in the nucleus accumbens (NAc). MS + SI female mice had significantly lower D1 receptor mRNA and protein levels than controls, whereas the expression of TH and the D2 receptor was similar in the 2 groups. All mRNA and protein levels were unchanged in MS + SI male mice. When attempting to elucidate the mechanism underlying downregulation of the D1 receptor in the NAc of MS + SI females, we found hypermethylation of the Drd1a promoter region. These results suggest that early-life stress affects reward-seeking behavior in female mice, which may be associated with the downregulation of D1 receptor in the NAc via epigenetic modification of its promoter region.
博士（医学）・甲第672号・平成29年6月28日
Copyright © 2017 Elsevier B.V. All rights reserved.
identifier:Neuroscience letters Vol.641 p.33-39 (2017 Feb)
identifier:03043940
identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3344
identifier:Neuroscience letters, 641: 33-39
DOIinfo:doi/10.1016/j.neulet.2017.01.025
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