促肾上腺皮质激素释放因子-1受体拮抗剂可减少长时程而非短时程获取海洛因的大鼠的海洛因自我给药行为。
Corticotropin-releasing factor-1 receptor antagonists decrease heroin self-administration in long- but not short-access rats.
作者信息
Greenwell Thomas N, Funk Cindy K, Cottone Pietro, Richardson Heather N, Chen Scott A, Rice Kenner C, Zorrilla Eric P, Koob George F
机构信息
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, USA.
出版信息
Addict Biol. 2009 Apr;14(2):130-43. doi: 10.1111/j.1369-1600.2008.00142.x.
Dysregulation of the stress-related corticotropin-releasing factor (CRF) system has been implicated in the development of drug dependence. The present study examined the effects of administering CRF type 1 (CRF(1)) receptor antagonists on heroin self-administration in animals allowed short (1 hour) or long (8-12 hours) access to intravenous heroin self-administration sessions. The nonpeptide CRF(1) antagonists MJL-1-109-2 (1 hour versus 8 hours access) or R121919 (1 hour versus 12 hours access) were systemically injected in both short- and long-access rats. MJL-1-109-2 (10 mg/kg) and R121919 (10 and 20 mg/kg) reduced heroin self-administration in long-access animals without altering heroin intake in short-access animals. Both MJL-1-109-2 and R121919 decreased first-hour intravenous heroin self-administration selectively in long-access rats, with R121919 decreasing cumulative heroin intake across the 12-hour session. The results demonstrate that blockade of the CRF-CRF(1) receptor system attenuates the increased heroin intake of rats with extended access to the drug.
与应激相关的促肾上腺皮质激素释放因子（CRF）系统失调与药物依赖的发展有关。本研究考察了给予1型CRF（CRF(1)）受体拮抗剂对动物海洛因自我给药的影响，这些动物可进行短时间（1小时）或长时间（8 - 12小时）的静脉注射海洛因自我给药实验。非肽类CRF(1)拮抗剂MJL - 1 - 109 - 2（1小时给药与8小时给药对比）或R121919（1小时给药与12小时给药对比）被分别全身注射到短时间给药和长时间给药的大鼠体内。MJL - 1 - 109 - 2（10毫克/千克）和R121919（10毫克/千克和20毫克/千克）减少了长时间给药动物的海洛因自我给药量，而未改变短时间给药动物的海洛因摄入量。MJL - 1 - 109 - 2和R121919均选择性地减少了长时间给药大鼠第一小时的静脉注射海洛因自我给药量，其中R121919还减少了12小时实验期间的累积海洛因摄入量。结果表明，阻断CRF - CRF(1)受体系统可减弱长时间接触药物的大鼠增加的海洛因摄入量。
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