期刊
NEUROPSYCHOPHARMACOLOGY
卷 35, 期 6, 页码 1241-1252出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2009.209
关键词
drinking in the dark; CRF receptor; HPA axis; binge drinking; ethanol consumption; C57BL/6J mice
资金
- NIH [AA017803, A1AA013573, AA015148, AA014983, AA011605, AA016629]
- Department of Defense [W81XWH-06-1-0158, W81XWH-09-1-0293]
Recent evidence suggests that corticotropin-releasing factor (CRF) receptor (CRFR) signaling is involved in modulating binge-like ethanol consumption in C57BL/6J mice. In this report, a series of experiments were performed to further characterize the role of CRFR signaling in binge-like ethanol consumption. The role of central CRFR signaling was assessed with intracerebroventricular (i.c.v.) infusion of the nonselective CRFR antagonist, alpha-helical CRF9-41 (0, 1, 5, 10 mu g/l mu l). The contribution of central CRF type 2 receptor (CRF2R) signaling was assessed with i.c.v. infusion of the selective CRF2R agonist, urocortin (Ucn) 3 (0, 0.05, 0.1, or 0.5 mu g/l mu l). The role of the hypothalamic-pituitary-adrenal (HPA) axis was assessed by pretreating mice with intraperitoneal (i.p.) injection of (1) the corticosterone synthesis inhibitor, metyrapone (0, 50, 100, 150 mg/kg) or (2) the glucocorticoid receptor antagonist, mifepristone (0, 25, 50 mg/kg), and (3) by using radioimmunoassay to determine whether binge-like ethanol intake influenced plasma corticosterone levels. Finally, we determined whether the ability of the CRF1R antagonist, CP-154,526 (CP; 0, 10, 15 mg/kg, i.p.), to blunt binge-like drinking required normal HPA axis signaling by comparing the effectiveness of CP in adrenalectomized (ADX) and normal mice. Results showed that i.c.v. infusion of a 1 mu g dose of a-helical CRF9-41 significantly attenuated binge-like ethanol consumption relative to vehicle treatment, and i.c.v. infusion of Ucn 3 dose-dependently blunted binge-like drinking. On the other hand, metyrapone nonselectively reduced both ethanol and sucrose consumption, mifepristone did not alter ethanol drinking, and binge-like drinking did not correlate with plasma corticosterone levels. Finally, i.p. injection of CP significantly attenuated binge-like ethanol intake in both ADX and normal mice. Together, these results suggest that binge-like ethanol intake in C57BL/6J mice is modulated by CRF1R and CR(F)2R signaling, such that blockade of CRF1R or activation of CRF2R effectively reduces excessive ethanol intake. Furthermore, normal HPA axis signaling is not necessary to achieve binge-like drinking behavior. Neuropsychopharmacology (2010) 35, 1241-1252; doi: 10.1038/npp.2009.209; published online 3 February 2010
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据