Suppression of reward-induced dopamine release in the nucleus accumbens in animal models of depression: Differential responses to drug treatment
Suppression of reward-induced dopamine release in the nucleus accumbens in animal models of depression: Differential responses to drug treatment
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DOI：
10.1016/j.neulet.2017.04.028
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发表时间：
2017-05-22
影响因子：
2.5
通讯作者：
Minami, Masabumi
中科院分区：
文献类型：
--
作者：
Minami, Saki;Satoyoshi, Hiroshi;Minami, Masabumi
快感缺乏，即对以前愉快的活动失去兴趣或乐趣，是重度抑郁症的核心症状，表明在这种情况下大脑奖励系统可能功能失调。在抑郁症动物模型中，中脑边缘多巴胺（DA）系统的神经化学变化尚未完全了解。我们在两种抑郁症动物模型中研究了奖赏（摄入 30% 蔗糖）诱导的伏核 (NAc) 中 DA 释放以及抗抑郁药艾司西酞普兰（5 mg/kg，腹腔注射，每天两次，持续 3 周）长期治疗的效果。成年期暴露于慢性轻度应激 (CMS) 完全抑制了奖赏诱导的 NAc 内 DA 释放；然而，长期服用艾司西酞普兰治疗可以逆转这种效应。我们的研究结果表明，奖励诱导的 NAc 内 DA 释放可能是抑郁症严重程度和治疗效果的指标。新生儿母体分离 (MS) 和成年期 CMS 的暴露完全抑制了奖赏诱导的 NAc 内 DA 释放。艾司西酞普兰的长期治疗并没有恢复这些动物中奖赏诱导的 DA 释放，这表明这种范例可以作为难治性抑郁症的动物模型。对这些抑郁症动物模型中脑边缘多巴胺能系统的进一步研究可能会阐明抑郁症和治疗抵抗的神经机制。 (C) 2017 Elsevier B.V. 保留所有权利。
Anhedonia, the loss of interest or pleasure in previously enjoyable activities, is a core symptom of major depressive disorder, suggesting that the brain reward system may be dysfunctional in this condition. Neurochemical changes in the mesolimbic dopamine (DA) system are not fully understood in animal models of depression. We investigated reward (30% sucrose intake)-induced DA release in the nucleus accumbens (NAc) and the effect of chronic treatment with the antidepressant escitalopram (5 mg/kg, intraperitoneally twice daily for 3 weeks) in two animal models of depression. Exposure to chronic mild stress (CMS) during adulthood completely suppressed reward-induced intra-NAc DA release; however, this effect was reversed by chronic treatment with escitalopram. Our findings suggest that reward-induced intra-NAc DA release may be an indicator of depression severity and therapeutic efficacy. Exposure to neonatal maternal separation (MS) and CMS in adulthood completely suppressed reward-induced intra-NAc DA release. Chronic treatment with escitalopram did not restore reward-induced DA release in these animals, suggesting that this paradigm may serve as an animal model for treatment-resistant depression. Further study of the mesolimbic dopaminergic system in these animal models of depression may clarify the neural mechanisms underlying depression and treatment resistance. (C) 2017 Elsevier B.V. All rights reserved.