Involvement of dopamine D2 receptor in a single methamphetamine-induced behavioral sensitization in C57BL/6J mice
Involvement of dopamine D2 receptor in a single methamphetamine-induced behavioral sensitization in C57BL/6J mice
复制标题
多巴胺 D2 受体参与 C57BL/6J 小鼠单一甲基苯丙胺诱导的行为敏化
DOI：
10.1016/j.neulet.2018.02.067
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发表时间：
2018-08-10
影响因子：
2.5
通讯作者：
Liang, Jian-Hui
中科院分区：
文献类型：
--
作者：
Jing, Li;Liu, Ben;Liang, Jian-Hui
单一接触滥用药物足以诱导行为敏化，这是一种长期神经塑性的形式。多巴胺D2受体是抗精神病药的主要受体，但对它们在单个甲基苯丙胺诱导的行为敏化中的作用知之甚少。在本研究中，我们检查了典型的抗精神病药氟哌啶醇和非典型抗精神病药物（均针对多巴胺D2受体）是否可以防止在行为敏化的不同阶段给出甲基苯丙胺敏化。单一的甲基苯丙胺暴露在无药物期7天后引起甲基苯丙胺的较低挑战剂量引起稳健和可靠的行为敏化。在不影响一般运动的剂量下，氟哌啶醇和利培酮不仅显着减弱甲基苯丙胺诱导的超量敏性，而且还完全阻止了在首次暴露于甲基苯丙胺之前对甲基苯丙胺挑战的行为敏化的发展。当在转移的早期（第一次甲基苯丙胺暴露后2小时）给出氟哌啶醇和利培酮时，它们还剂量依赖性地降低了从多型敏感的甲基苯丙胺敏化表达的转移。这些数据表明，多巴胺D2受体在甲基苯丙胺致敏中起重要作用，尤其是在甲基苯丙胺暴露后的早期不稳定时期预防发育和转移方面。因此，经临床认可的多巴胺D2受体拮抗剂可能有用，可用于治疗甲基苯丙胺成瘾。
A single exposure to drugs of abuse is sufficient to induce behavioral sensitization, which is a form of long-lasting neuroplasticity. Dopamine D2 receptors are the main receptor for antipsychotic drugs, but little is known about their role in a single methamphetamine-induced behavioral sensitization. In the present study, we examined whether typical antipsychotic haloperidol and atypical antipsychotic risperidone, both targeting dopamine D2 receptor, could prevent the methamphetamine sensitization when they were given at the different phase of behavioral sensitization. A single methamphetamine exposure induced robust and reliable behavioral sensitization to the lower challenge dose of methamphetamine after 7 days of drug-free period. At doses that did not affect general locomotion, haloperidol and risperidone not only significantly attenuated methamphetamine induced hyperlocomotion, but also completely prevented the development of behavioral sensitization to methamphetamine challenge when they were pretreated before the first exposure to methamphetamine. When haloperidol and risperidone were given in the early period of transfer (2 h after the first methamphetamine exposure), they also dose-dependently attenuated the transfer to expression of methamphetamine sensitization from the hyperlocomotion. These data suggest that dopamine D2 receptors play an important role in methamphetamine sensitization, especially in protecting against the development and transfer in the earlier labile period after the methamphetamine exposure. Therefore, clinically approved dopamine D2 receptor antagonists may be useful in the treatment of methamphetamine addiction.