Effects of the Trace Amine Associated Receptor 1 Agonist RO5263397 on Abuse-Related Behavioral Indices of Methamphetamine in Rats
Effects of the Trace Amine Associated Receptor 1 Agonist RO5263397 on Abuse-Related Behavioral Indices of Methamphetamine in Rats
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DOI：
10.1093/ijnp/pyu060
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发表时间：
2015-02-01
影响因子：
4.8
通讯作者：
Li, Jun-Xu
中科院分区：
文献类型：
--
作者：
Jing, Li;Zhang, Yanan;Li, Jun-Xu
背景：甲基苯丙胺是一种主要的滥用药物，目前尚无有效的药物治疗方法。微量胺相关受体1与可卡因成瘾有关，是一个潜在的治疗靶点。然而，微量胺相关受体1激动剂对甲基苯丙胺成瘾相关行为的影响尚不清楚。方法：研究微量胺相关受体1激动剂RO5263397对大鼠甲基苯丙胺诱导的行为致敏、甲基苯丙胺自我给药、线索和甲基苯丙胺诱导的药物寻求恢复以及线索诱导的蔗糖寻求行为恢复的影响。雄性Sprague-Dawley大鼠单用甲基苯丙胺及与微量胺相关受体1激动剂RO5263397 （3.2-10 mg/kg）联合使用对大鼠的影响。结果：RO5263397剂量依赖性地减弱了对甲基苯丙胺行为敏感性的表达，减少了甲基苯丙胺自我给药，并降低了甲基苯丙胺诱导的药物寻求行为恢复的提示剂量和启动剂量。然而，RO5263397并没有改变线索诱导的蔗糖寻求行为的恢复。结论：综上所述，微量胺相关受体1激动剂可以减弱甲基苯丙胺滥用相关的行为效应，这强烈表明，激活微量胺相关受体1的药物可能对甲基苯丙胺成瘾的治疗有潜在的作用，值得进一步研究。
Background: Methamphetamine is a major drug of abuse with no effective pharmacotherapy available. Trace amine associated receptor 1 is implicated in cocaine addiction and represents a potential therapeutic target. However, the effects of trace amine associated receptor 1 agonists on addiction-related behavioral effects of methamphetamine are unknown.Methods: This study examined the effects of a trace amine associated receptor 1 agonist RO5263397 on methamphetamineinduced behavioral sensitization, methamphetamine self-administration, cue-and methamphetamine-induced reinstatement of drug seeking, and cue-induced reinstatement of sucrose-seeking behaviors in rats. Male Sprague-Dawley rats were used to examine the effects of methamphetamine alone and in combination with the trace amine associated receptor 1 agonist RO5263397 (3.2-10 mg/kg).Results: RO5263397 dose-dependently attenuated the expression of behavioral sensitization to methamphetamine, reduced methamphetamine self-administration, and decreased both cue-and a priming dose of methamphetamine-induced reinstatement of drug-seeking behaviors. However, RO5263397 did not alter cue-induced reinstatement of sucrose-seeking behavior.Conclusions: Taken together, trace amine associated receptor 1 agonists attenuate some abuse-related behavioral effects of methamphetamine, strongly suggesting that drugs activating trace amine associated receptor 1 may be potentially useful for the treatment of methamphetamine addiction and warrant further studies.