Use of intracranial self-stimulation to evaluate abuse-related and abuse-limiting effects of monoamine releasers in rats
Use of intracranial self-stimulation to evaluate abuse-related and abuse-limiting effects of monoamine releasers in rats
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DOI：
10.1111/j.1476-5381.2012.02214.x
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发表时间：
2013-02-01
影响因子：
7.3
通讯作者：
Negus, S. S.
中科院分区：
文献类型：
--
作者：
Bauer, C. T.;Banks, M. L.;Negus, S. S.
背景技术单胺释放剂构成一类促进多巴胺（DA）、5-羟色胺（5-HT）和/或去甲肾上腺素释放的药物。虽然这类药物中有些是众所周知的滥用药物（安非他明、甲基安非他明），但其他药物被认为具有减少的（3，4-亚甲二氧基-N-甲基安非他明[MDMA]）或没有（芬氟拉明）滥用潜力。本研究的目的是进一步阐明多巴胺与5-羟色胺选择性对大鼠颅内自我刺激（ICSS）测定中单胺释放剂产生的滥用相关效应的表达的作用。实验方法本研究评价了11种单胺释放剂在频率-速率ICSS程序中产生的效应，这些单胺释放剂对释放DA与5-羟色胺的选择性不同。HT.关键提示单胺释放剂促进ICSS的功效与DA选择性相关，例如DA选择性释放剂仅促进ICSS，5-HT选择性释放剂仅抑制ICSS，混合作用释放剂既促进低ICSS率又抑制高ICSS率。DA选择性释放剂和5-HT选择性释放剂的固定比例混合物概括了混合作用释放剂的效果。单胺释放剂促进ICSS的功效也与先前发表的关于维持恒河猴自我给药的功效的数据相关，恒河猴在强化的累进比时间表下响应。滥用相关影响的管理措施。总之，这些结果支持使用ICSS在大鼠中作为一种实验工具，以研究滥用相关的单胺释放剂的影响的表达和药理学决定因素。
BACKGROUND AND PURPOSEMonoamine releasers constitute a class of drugs that promote the release of dopamine (DA), serotonin (5-HT) and/or norepinephrine. Although some drugs in this class are well-known drugs of abuse (amphetamine, methamphetamine), others are thought to have reduced (3,4-methylenedioxy-N-methylamphetamine [MDMA]) or no (fenfluramine) abuse potential. The purpose of this study was to further elucidate the role of dopamine versus serotonin selectivity on expression of abuse-related effects produced by monoamine releasers in an assay of intracranial self-stimulation (ICSS) in rats.EXPERIMENTAL APPROACHThis study evaluated effects produced in a frequency-rate ICSS procedure by 11 monoamine releasers that vary in selectivity to release DA versus 5-HT.KEY RESULTSEfficacy of monoamine releasers to facilitate ICSS correlated with DA-selectivity, such that DA-selective releasers exclusively facilitated ICSS, a 5-HT-selective releaser exclusively depressed ICSS, and mixed-action releasers both facilitated low ICSS rates and depressed high ICSS rates. Fixed-proportion mixtures of a DA-selective releaser and a 5-HT-selective releaser recapitulated effects of mixed-action releasers. Efficacy of monoamine releasers to facilitate ICSS also correlated with previously published data on efficacy to maintain self-administration in rhesus monkeys responding under a progressive-ratio schedule of reinforcement.CONCLUSIONS AND IMPLICATIONSThese data support the importance of selectivity for DA versus 5-HT in determining abuse potential of monoamine releasers and demonstrate a novel correlation between rat ICSS and nonhuman primate self-administration measures of abuse-related effects. Taken together, these results support the use of ICSS in rats as an experimental tool to study the expression and pharmacological determinants of abuse-related effects of monoamine releasers.