Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5738501 | Neuroscience Letters | 2017 | 7 Pages |
Abstract
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) (MSÂ +Â SI) is widely used as a model for early-life stress in rodent studies. We employed mice subjected to MSÂ +Â 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 MSÂ +Â 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). MSÂ +Â 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 MSÂ +Â SI male mice. When attempting to elucidate the mechanism underlying downregulation of the D1 receptor in the NAc of MSÂ +Â 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.
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Authors
Takayo Sasagawa, Noriko Horii-Hayashi, Akinori Okuda, Takashi Hashimoto, Cho Azuma, Mayumi Nishi,