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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >SA 4503 attenuates cocaine-induced hyperactivity and enhances methamphetamine substitution for a cocaine discriminative stimulus.
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SA 4503 attenuates cocaine-induced hyperactivity and enhances methamphetamine substitution for a cocaine discriminative stimulus.

机译：SA 4503减弱了可卡因诱导的机能亢进，并增强了甲基苯丙胺对可卡因的歧视性刺激的替代作用。

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摘要

Cocaine exhibits preferential (~15-fold) affinity for sigma over sigma sigma receptors, and previous research has shown an interaction of sigma receptor-selective ligands and cocaine's behavioral effects. The present study investigated the effect of the putative sigma receptor agonist SA 4503 (1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride) on cocaine's locomotor stimulatory and discriminative stimulus properties. At doses without intrinsic activity, SA 4503 dose-dependently attenuated cocaine-induced hyperactivity in mice. This inhibition was overcome by increasing the cocaine dose. In rats trained to use cocaine as a discriminative stimulus in a drug discrimination task, doses of SA 4503 that did not substitute for the cocaine stimulus did not alter the cocaine substitution curve. However, SA 4503 potentiated the effect of methamphetamine to substitute for the cocaine stimulus. These data support a role for sigma receptors in the locomotor-activating properties of cocaine and, importantly, indicate a role for these receptors in the discriminative stimulus effects of methamphetamine. The data also suggest sigma receptors mediate the activity of different dopamine pathways responsible for the behavioral effects of psychostimulants.
机译：可卡因对sigma的亲和力比sigma sigma受体高（约15倍），并且以前的研究表明sigma受体选择性配体与可卡因的行为效应相互作用。本研究调查了假定的sigma受体激动剂SA 4503（1-（3，4-二甲氧基苯乙基）-4-（3-苯基丙基）哌嗪二盐酸盐）对可卡因运动刺激和判别刺激特性的影响。在没有内在活性的剂量下，SA 4503剂量依赖性地减轻了可卡因诱导的小鼠活动过度。通过增加可卡因剂量可以克服这种抑制作用。在接受过训练以在药物区分任务中使用可卡因作为判别刺激的大鼠中，不能替代可卡因刺激的剂量的SA 4503不会改变可卡因替代曲线。但是，SA 4503增强了甲基苯丙胺替代可卡因刺激的作用。这些数据支持西格玛受体在可卡因的运动激活特性中的作用，并且重要地表明这些受体在甲基苯丙胺的歧视性刺激作用中的作用。数据还表明，sigma受体介导了引起精神兴奋剂行为影响的不同多巴胺途径的活性。

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