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苯丙胺自我给药中的个体差异:杏仁核中央核的作用。

Individual differences in amphetamine self-administration: the role of the central nucleus of the amygdala.

作者信息

Cain Mary E, Denehy Emily D, Bardo Michael T

机构信息

Department of Psychology, Kansas State University, Manhattan, KS 66506-5302, USA.

出版信息

Neuropsychopharmacology. 2008 Apr;33(5):1149-61. doi: 10.1038/sj.npp.1301478. Epub 2007 Jun 13.

Abstract

Rats categorized as high responder (HR), based on their activity in an inescapable novel environment, self-administer more amphetamine than low responder (LR) rats. The current study examined if the central nucleus of the amygdala (ACe) contributes to the elevated response for amphetamine in HR rats. Male Sprague-Dawley rats were classified as HR and LR rats based on their activity in inescapable novelty and novelty place preference, and then were trained to self-administer amphetamine (0.1 mg/kg/infusion). Once stable responding was achieved, rats received microinfusions of the GABA(A) agonist muscimol (0.5 microg/0.5 microl) or phosphate-buffered saline into the ACe immediately before self-administration of amphetamine (0.1, 0.03, 0.01, or 0.001 mg/kg/infusion) or saline. An additional group of rats was trained to lever press for sucrose rather than amphetamine. Based on the inescapable novelty test, HR rats self-administered more amphetamine than LR rats at the 0.03 and 0.01 mg/kg/infusion unit doses; there were no significant individual differences in amphetamine self-administration based on the novelty place preference test. Inactivation of the ACe with muscimol decreased self-administration at the 0.03 and 0.01 mg/kg/infusion unit doses in HR rats, but had no effect on LR rats. ACe inactivation had no reliable effect on inactive lever responding and appeared to be region specific based on anatomical controls. In addition, while inactivation of the ACe decreased responding for sucrose, inactivation did not differentially affect HR and LR rats. These results suggest that the ACe contributes to the elevated rate of amphetamine self-administration in HR rats.

摘要

根据大鼠在不可逃避的新环境中的活动情况,将其分类为高反应者(HR),与低反应者(LR)相比,HR大鼠自我给药的苯丙胺更多。本研究探讨了杏仁核中央核(ACe)是否导致HR大鼠对苯丙胺的反应增强。根据雄性Sprague-Dawley大鼠在不可逃避的新奇环境中的活动情况以及新奇环境偏好,将其分为HR和LR大鼠,然后训练它们自我给药苯丙胺(0.1毫克/千克/输注)。一旦达到稳定反应,在大鼠自我给药苯丙胺(0.1、0.03、0.01或0.001毫克/千克/输注)或生理盐水之前,立即向其ACe内微量注射GABA(A)激动剂蝇蕈醇(0.5微克/0.5微升)或磷酸盐缓冲盐水。另一组大鼠接受训练,通过按压杠杆获取蔗糖而非苯丙胺。根据不可逃避的新奇性测试,在0.03和0.01毫克/千克/输注单位剂量下,HR大鼠自我给药的苯丙胺比LR大鼠更多;根据新奇环境偏好测试,在苯丙胺自我给药方面没有显著的个体差异。用蝇蕈醇使ACe失活会降低HR大鼠在0.03和0.01毫克/千克/输注单位剂量下的自我给药量,但对LR大鼠没有影响。ACe失活对非活性杠杆反应没有可靠影响,且根据解剖学对照似乎具有区域特异性。此外,虽然ACe失活会降低对蔗糖的反应,但失活对HR和LR大鼠没有差异影响。这些结果表明,ACe导致HR大鼠苯丙胺自我给药率升高。

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