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通过抑制海马体钙/钙调蛋白依赖性蛋白激酶II的活性来损害大鼠的苯丙胺条件反射。

Impairing the amphetamine conditioning in rats through the inhibition of hippocampal calcium/calmodulin-dependent protein kinase II activity.

作者信息

Tan S-E

机构信息

Department of Psychology, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan, ROC.

出版信息

Neuropharmacology. 2002 Mar;42(4):540-7. doi: 10.1016/s0028-3908(02)00004-7.

DOI:10.1016/s0028-3908(02)00004-7
PMID:11955524
Abstract

Amphetamine is an addictive drug, possessing reinforcing properties that are believed to be associated with an environmental cue, which resembles a behavioral learning process. This study investigates the role of calcium/calmodulin-dependent protein kinase II (CaM-kinase II) in the acquisition of the amphetamine-produced conditioned place preference (CPP). In Experiment I, rats were trained in an amphetamine-produced (2 mg/kg, i.p.) CPP task. The amphetamine-saline pairing rats spent significantly more time in the box that was associated with the amphetamine injection. Moreover, these rats' hippocampal CaM-kinase II showed significantly higher Ca(2+)-independent activity than that of the controls. In experiment II, the rats received an intra-hippocampal or intra-accumbens injection of specific CaM-kinase II inhibitor (KN-93) or a controlled agent (KN-92) before training in the amphetamine-produced CPP task. The rats receiving the preconditioning intra-hippocampal KN-93 injection showed no amphetamine-produced CPP effect. These results, taken together, indicate that the biological basis of amphetamine-produced place preference behavior might be regulated by the hippocampal CaM-kinase II activity.

摘要

苯丙胺是一种成瘾性药物,具有强化特性,这种特性被认为与一种环境线索有关,这类似于一种行为学习过程。本研究调查钙/钙调蛋白依赖性蛋白激酶II(CaM-激酶II)在苯丙胺诱导的条件性位置偏爱(CPP)获得过程中的作用。在实验I中,大鼠接受苯丙胺诱导(2毫克/千克,腹腔注射)的CPP任务训练。苯丙胺-生理盐水配对组大鼠在与苯丙胺注射相关的盒子里停留的时间明显更长。此外,这些大鼠海马体中的CaM-激酶II显示出比对照组明显更高的非钙依赖性活性。在实验II中,大鼠在接受苯丙胺诱导的CPP任务训练前,海马体内或伏隔核内注射特异性CaM-激酶II抑制剂(KN-93)或对照剂(KN-92)。接受海马体预处理KN-93注射的大鼠未表现出苯丙胺诱导的CPP效应。综合这些结果表明,苯丙胺诱导的位置偏爱行为的生物学基础可能受海马体CaM-激酶II活性的调节。

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