多巴胺D3受体激动剂和拮抗剂减弱甲基苯丙胺诱导的行为敏化

Dopamine D3 receptor agonist and antagonist attenuate methamphetamine-induced behavioral sensitization

目的通过研究多巴胺D3受体(dopamine D3 receptor,D3R)激动剂ML417和拮抗剂GSK598809对甲基苯丙胺(methamphetamine,METH)诱导的小鼠行为敏化的影响,探讨D3R在METH成瘾中的调控作用。方法以D3R基因敲除(D3R-/-)小鼠以及具有相同遗传背景的野生型(WT)小鼠为研究对象,采用行为敏化模型,观测D3R激动剂ML417和拮抗剂GSK598809对METH诱导的行为敏化的影响。结果D3R激动剂ML417(1 mg/kg,ip)和拮抗剂GSK598809(5 mg/kg、10 mg/kg,ip)均可减弱METH(2 mg/kg,ip)诱导的WT小鼠行为敏化(P<0.05),但在对照组D3R-/-小鼠中并无此作用。结论D3R激动剂ML417和拮抗剂GSK598809均可通过单一激动或拮抗D3R的方式,减弱METH诱导的WT小鼠行为敏化,D3R可能成为治疗METH成瘾的一个靶点。

Objective To explore the regulatory roles of D3R in METH addiction and the effects of dopamine D3 receptor(D3R)agonist ML417 and antagonist GSK598809 on methamphetamine(METH)-induced behavioral sensitization in mice.Methods Wild-type(WT)and D3R knockout(D3R-/-)mice with the same genetic background were used to observe the effects of D3R agonist ML417 and antagonist GSK598809 on METH-induced behavioral sensitization.Results Both D3R agonist ML417(1 mg/kg,ip)and antagonist GSK598809(5 mg/kg,10 mg/kg,ip)could attenuate METH(2 mg/kg,ip)-induced behavioral sensitization in WT mice(P<0.05),but not in D3R-/-mice.Conclusion Both the D3R agonist ML417 and the antagonist GSK598809 can attenuate METH-induced behavioral sensitization in WT mice by agonizing or antagonizing D3R alone,and D3R may become a target for the treatment of METH addiction.