Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
Neuropharmacology. 2019 Jun;151:13-20. doi: 10.1016/j.neuropharm.2019.03.017. Epub 2019 Mar 25.
The recreational drug 3,4-methylenedioxymethamphetamine (MDMA) has well documented prosocial effects and is currently under clinical investigation as a treatment for patients with PTSD, autism, and other conditions. Early clinical trials have found that MDMA-assisted therapy may have robust long-lasting therapeutic effects, yet the mechanism by which acute treatments produce these long-term effects is unclear. Sensitization to certain behavioral drug effects is a common rodent model used to assess long-lasting neurobiological adaptations induced by acute drug treatments. Nine independent experiments were undertaken to investigate if and how mice sensitize to the prosocial effects of MDMA. When treated with 7.8 mg/kg MDMA and paired every other day for a week, MDMA-induced social interaction increased precipitously across treatment sessions. This previously unreported phenomenon was investigated and found to be heavily influenced by a social context and 5-HTR activation. Social sensitization did not appear to develop if mice were administered MDMA in isolation, and pretreatment with MDL100907, a selective 5-HTR antagonist, inhibited the development of social sensitization. However, when MDL100907 was administered to mice that had already been sensitized, it did not attenuate social interaction, suggesting that 5-HTR activity may be necessary for the development of social sensitization but not the expression of MDMA-induced social behavior. Additional investigation is warranted to further explore the phenomenon of social sensitization and to determine the underlying neurobiological mechanisms.
娱乐性毒品 3,4-亚甲二氧基甲基苯丙胺（MDMA）具有良好的社交促进作用，目前正在临床研究中，作为治疗创伤后应激障碍、自闭症和其他疾病的方法。早期临床试验发现，MDMA 辅助治疗可能具有强大的持久治疗效果，但急性治疗产生这些长期效果的机制尚不清楚。对某些行为药物效应的敏感化是一种常用的啮齿动物模型，用于评估急性药物治疗引起的持久神经生物学适应性。进行了九项独立的实验，以研究老鼠是否会对 MDMA 的社交促进作用产生敏感。当用 7.8mg/kg 的 MDMA 治疗，并每隔一天配对治疗一周时，MDMA 诱导的社交互动在治疗过程中急剧增加。这是一个以前未报道过的现象，经过研究发现，它受到社会环境和 5-HTR 激活的强烈影响。如果老鼠单独给予 MDMA，则不会出现社交敏感化，而选择性 5-HTR 拮抗剂 MDL100907 的预处理则抑制了社交敏感化的发展。然而，当 MDL100907 给予已经敏感化的老鼠时，它并没有减弱社交互动，这表明 5-HTR 活性可能是社交敏感化发展所必需的，但不是 MDMA 诱导的社交行为表达所必需的。需要进一步研究来进一步探索社交敏感化现象，并确定潜在的神经生物学机制。
