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Anhedonia requires MC4R-mediated synaptic adaptations in nucleus accumbens

机译：快感缺乏症需要伏伏核中MC4R介导的突触适应

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摘要

Chronic stress is a strong diathesis for depression in humans and is used to generate animal models of depression. It commonly leads to several major symptoms of depression, including dysregulated feeding behaviour, anhedonia and behavioural despair. Although hypotheses defining the neural pathophysiology of depression have been proposed, the critical synaptic adaptations in key brain circuits that mediate stress-induced depressive symptoms remain poorly understood. Here we show that chronic stress in mice decreases the strength of excitatory synapses on D1 dopamine receptor-expressing nucleus accumbens medium spiny neurons owing to activation of the melanocortin 4 receptor. Stress-elicited increases in behavioural measurements of anhedonia, but not increases in measurements of behavioural despair, are prevented by blocking these melanocortin 4 receptor-mediated synaptic changes in vivo. These results establish that stress-elicited anhedonia requires a neuropeptide-triggered, cell-type-specific synaptic adaptation in the nucleus accumbens and that distinct circuit adaptations mediate other major symptoms of stress-elicited depression.
机译：慢性应激是人类抑郁症的强大素质，可用于生成抑郁症的动物模型。它通常会导致抑郁的几种主要症状，包括进食行为失调，快感不足和行为绝望。尽管提出了定义抑郁症的神经病理生理学的假说，但对于调解压力引起的抑郁症状的关键脑回路中关键的突触适应仍然知之甚少。在这里，我们显示，由于黑素皮质素4受体的激活，小鼠的慢性应激会降低D1多巴胺受体表达的伏隔核中突棘神经元上兴奋性突触的强度。通过阻断体内这些黑皮质素4受体介导的突触变化，可以防止应激引起的性欲低下，但没有提高行为绝望的行为。这些结果表明，应激引起的性快感缺乏需要伏伏核中神经肽触发的细胞类型特异性突触适应，并且不同的回路适应介导了应激引起的抑郁症的其他主要症状。

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  • 来源
    《Nature》 |2012年第7406期|p.183-189|共7页
  • 作者

    Byung Kook Lim; Kee Wui Huang; Brad A. Grueter; Patrick E. Rothwell; Robert C. Malenka;

  • 作者单位

    Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, California 94305, USA;

    Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, California 94305, USA;

    Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, California 94305, USA;

    Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, California 94305, USA;

    Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, California 94305, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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