CRF2 receptor-deficiency eliminates opiate withdrawal distress without impairing stress coping
CRF2 receptor-deficiency eliminates opiate withdrawal distress without impairing stress coping
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DOI：
10.1038/mp.2011.119
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发表时间：
2012-12-01
影响因子：
11
通讯作者：
Contarino, A.
中科院分区：
文献类型：
--
作者：
Ingallinesi, M.;Rouibi, K.;Contarino, A.
阿片类药物戒断综合征是一种严重的应激源，强烈地触发成瘾药物的摄入。然而，目前还没有有效缓解阿片类药物戒断痛苦和保留压力应对能力的治疗方法。促肾上腺皮质激素释放因子（CRF）系统介导的应激反应，但它的作用阿片类药物戒断痛苦和身体的策略，旨在科普是未知的。CRF样信号通过两种受体途径传递，称为CRF 1和CRF 2。在这里，我们报告说，CRF 2受体缺陷（CRF 2-/-）小鼠缺乏焦虑样和快感缺乏样阿片类药物戒断状态。此外，在CRF 2-/-小鼠中，阿片戒断并不增加脑强啡肽、CRF和导水管周围灰质回路的活性，这些是阿片戒断痛苦的主要底物。然而，CRF 2受体缺陷并不损害大脑，神经内分泌和自主神经压力应对阿片类药物戒断反应。目前的研究结果指出，CRF 2受体途径作为一个独特的目标，以减轻阿片类药物戒断痛苦，而不损害压力应对能力。Molecular Psychiatry（2012）17，1283-1294; doi：10.1038/mp.2011.119; 2011年9月27日在线发表
The opiate withdrawal syndrome is a severe stressor that powerfully triggers addictive drug intake. However, no treatment yet exists that effectively relieves opiate withdrawal distress and spares stress-coping abilities. The corticotropin-releasing factor (CRF) system mediates the stress response, but its role in opiate withdrawal distress and bodily strategies aimed to cope with is unknown. CRF-like signaling is transmitted by two receptor pathways, termed CRF1 and CRF2. Here, we report that CRF2 receptor-deficient (CRF2-/-) mice lack the dysphoria-like and the anhedonia-like states of opiate withdrawal. Moreover, in CRF2-/- mice opiate withdrawal does not increase the activity of brain dynorphin, CRF and periaqueductal gray circuitry, which are major substrates of opiate withdrawal distress. Nevertheless, CRF2 receptor-deficiency does not impair brain, neuroendocrine and autonomic stress-coping responses to opiate withdrawal. The present findings point to the CRF2 receptor pathway as a unique target to relieve opiate withdrawal distress without impairing stress-coping abilities. Molecular Psychiatry (2012) 17, 1283-1294; doi:10.1038/mp.2011.119; published online 27 September 2011