Cornish Jennifer L, Clemens Kelly J, Thompson Murray R, Callaghan Paul D, Dawson Bronwyn, McGregor Iain S
Neuropharmacology Laboratory, Department of Psychology, Macquarie University, Sydney, Australia.
J Psychopharmacol. 2008 Jan;22(1):100-10. doi: 10.1177/0269881107082286.
Methamphetamine is a drug that is often consumed at dance parties or nightclubs where the ambient temperature is high. The present study determined whether such high ambient temperatures alter intravenous methamphetamine self-administration in the rat. Male Hooded Wistar rats were trained to self-administer intravenous methamphetamine (0.1 mg/kg/infusion) under a fixed ratio 1 (FR1) or progressive ratio (PR) schedule of reinforcement at an ambient temperature of 23 +/- 1 degrees C. They were then given their daily self-administration session at a raised ambient temperature of 30 +/- 1 degrees C. Methamphetamine self-administration was increased at 30 degrees C under both FR1 and PR reinforcement schedules, with the latter effect indicating that heat enhances the motivation to obtain methamphetamine. High temperatures did not alter self-administration of the D1 receptor agonist SKF 82958 in methamphetamine-experienced rats suggesting some specificity in the methamphetamine effect. When rats were given access to drink isotonic saline solution during methamphetamine self-administration sessions they drank much more solution at 30 degrees C than 23 degrees C. However, availability of isotonic saline to drink did not alter the heat-induced facilitation of methamphetamine self-administration (PR schedule) indicating that the heat effect does not simply reflect increased motivation for intravenous fluids. Hyperthermia was evident in rats self-administering methamphetamine at high ambient temperatures and fluid consumption did not prevent this effect. Heat did not affect blood levels of methamphetamine, or its principal metabolite amphetamine indicating that the facilitatory effect of heat did not reflect altered methamphetamine pharmacokinetics. Overall, these results show that high ambient temperatures increase the reinforcing efficacy of methamphetamine and encourage higher levels of drug intake.
甲基苯丙胺是一种常在环境温度较高的舞会或夜总会中被使用的毒品。本研究确定了如此高的环境温度是否会改变大鼠静脉注射甲基苯丙胺的自我给药行为。雄性帽状Wistar大鼠在环境温度为23±1摄氏度的条件下，按照固定比例1（FR1）或累进比例（PR）强化程序接受训练，以自我静脉注射甲基苯丙胺（0.1毫克/千克/输注）。然后，在环境温度升高至30±1摄氏度的条件下，让它们进行每日的自我给药实验。在FR1和PR强化程序下，30摄氏度时甲基苯丙胺的自我给药量均增加，后一种效应表明高温增强了获取甲基苯丙胺的动机。高温并未改变甲基苯丙胺成瘾大鼠对D1受体激动剂SKF 82958的自我给药行为，这表明甲基苯丙胺的效应具有一定特异性。当大鼠在甲基苯丙胺自我给药实验期间可以饮用等渗盐溶液时，它们在30摄氏度时饮用的溶液量比在23摄氏度时多得多。然而，饮用等渗盐溶液并未改变高温诱导的甲基苯丙胺自我给药促进作用（PR程序），这表明高温效应并非仅仅反映对静脉补液的动机增加。在高环境温度下自我给药甲基苯丙胺的大鼠出现明显的体温过高，而液体摄入并不能预防这种效应。高温并未影响甲基苯丙胺的血药浓度或其主要代谢产物苯丙胺的血药浓度，这表明高温的促进作用并非反映甲基苯丙胺药代动力学的改变。总体而言，这些结果表明，高环境温度会增加甲基苯丙胺的强化效力，并促使更高水平的药物摄入。
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