Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Drug Design and Synthesis Section, Chemical Biology Research Branch, National Institute on Drug Abuse, and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
Drug Alcohol Depend. 2023 Sep 1;250:110917. doi: 10.1016/j.drugalcdep.2023.110917. Epub 2023 Aug 8.
Humans often administer psychostimulants in party or music festival settings characterized by warm ambient temperatures, which may impact drug effects; however, preclinical studies rarely investigate drug effects at multiple ambient temperatures. Work with 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxypyrovalerone (MDPV) suggests that the presence of a 3,4-methylenedioxy ring moiety may influence ambient temperature-dependent effects.
Locomotor activity and conditioned place preference dose-response curves were generated at 20±2°C for two amphetamine analogues (MDMA and methamphetamine [METH]) and two cathinone analogues (MDPV and α-pyrrolidinopentiophenone [αPVP]) in mice. Effects were then redetermined at 29±2°C for each drug and assay.
All four drugs elicited dose-dependent locomotor stimulation at the cool ambient temperature. At the warm ambient temperature, MDMA and MDPV produced sensitization to stereotypy, whereas METH and αPVP produced sensitization to locomotor activity. Regarding place conditioning, the warm ambient environment potentiated place preference elicited by doses of METH and αPVP that were sub-threshold in the cool ambient environment, but attenuated the effects of analogous doses of MDMA and MDPV.
These studies suggest that warmer ambient temperatures may potentiate typical stimulant effects for the drugs lacking the 3,4-methylenedioxy ring, but may potentiate the behaviorally toxic/adverse effects for the drugs containing a 3,4-methylenedioxy ring. Thus, preclinical abuse liability studies conducted at standard laboratory temperatures may not fully capture the effects of psychostimulants and highlight the need to model the environments in which drugs are typically used by humans.
人类经常在温暖环境温度下的派对或音乐节环境中服用苯丙胺类兴奋剂，这可能会影响药物的作用；然而，临床前研究很少在多个环境温度下研究药物的作用。与 3,4-亚甲二氧基甲基苯丙胺（MDMA）和 3,4-亚甲二氧基吡咯戊酮（MDPV）合作的研究表明，3,4-亚甲二氧基环部分的存在可能会影响环境温度依赖性的影响。
在 20±2°C 下为两种苯丙胺类似物（MDMA 和 methamphetamine [METH]）和两种卡他酮类似物（MDPV 和 α-吡咯戊酮[αPVP]）生成运动活动和条件性位置偏好剂量反应曲线。然后，在每个药物和测定的 29±2°C 下重新确定效应。
所有四种药物在凉爽的环境温度下均表现出剂量依赖性的运动刺激作用。在温暖的环境温度下，MDMA 和 MDPV 引起刻板行为的敏化，而 METH 和 αPVP 引起运动活动的敏化。关于位置条件作用，温暖的环境温度增强了在凉爽环境温度下阈下剂量的 METH 和 αPVP 引起的位置偏好，但减弱了类似剂量的 MDMA 和 MDPV 的作用。
这些研究表明，温暖的环境温度可能增强缺乏 3,4-亚甲二氧基环的药物的典型刺激作用，但可能增强含有 3,4-亚甲二氧基环的药物的行为毒性/不良反应。因此，在标准实验室温度下进行的临床前滥用倾向研究可能无法完全捕捉到苯丙胺类兴奋剂的作用，并强调需要模拟人类通常使用药物的环境。
