Psychostimulant reinforcement is mediated by stimulation of both dopamine (DA) D1-like and D2-like receptors, suggesting that pharmacotherapy agents with a dual DA receptor mechanism may be useful for managing psychostimulant abuse. (-)-Stepholidine (L-SPD) is a Chinese herbal extract that functions as a D1-like receptor agonist and D2-like receptor antagonist. L-SPD has been shown to attenuate the reinforcing effects of heroin; however, its effects on the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV) have not been examined. The current study determined the effects of L-SPD on reinstatement of MDPV-seeking behavior in the drug intravenous self-administration (IVSA) and conditioned place preference (CPP) paradigms. To determine whether the effects of L-SPD were specific to psychostimulant reinforcement, we also examined its effects on sucrose-seeking behavior. Using a locomotor activity assay, we tested the locomotor effects of L-SPD, as well as its effects on MDPV-induced hyperactivity. The results of a battery of in vitro binding and functional assays confirmed that L-SPD functioned as a D1-like receptor agonist and D2-like receptor antagonist. In behavioral experiments, L-SPD dose-dependently attenuated cue plus MDPV-primed reinstatement of MDPV-seeking behavior in the IVSA model. The highest dose of L-SPD also attenuated MDPV-primed reinstatement of MDPV CPP, as well as cue-induced reinstatement of sucrose-seeking. L-SPD had no significant locomotor effects, and did not modulate the robust hyperactivity induced by MDPV. The current findings show for the first time a robust reinstatement effect with MDPV, which can be reduced by L-SPD. These results establish a role for DA receptors in drug-seeking behavior for MDPV.

中文翻译：

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多巴胺D1受体激动剂和D2受体拮抗剂（-）-Stepholidine降低大鼠3,4-亚甲二氧基吡咯烷酮（MDPV）的寻药行为的恢复。

多巴胺（DA）D1样和D2样受体的刺激介导了精神兴奋剂的增强，这表明具有双重DA受体机制的药物治疗剂可能对管理精神兴奋剂滥用有用。（-）-Stepholidine（L-SPD）是一种中草药提取物，具有D1样受体激动剂和D2样受体拮抗剂的功能。L-SPD已显示减弱海洛因的增强作用。但是，尚未研究其对合成卡西酮3,4-亚甲基二氧基吡咯烷酮（MDPV）的影响。当前的研究确定了L-SPD在药物静脉自给药（IVSA）和条件性位置偏爱（CPP）范例中对MDPV寻求行为恢复的影响。为了确定L-SPD的作用是否专门针对心理刺激增强剂，我们还研究了其对寻求蔗糖行为的影响。使用运动活性测定法，我们测试了L-SPD的运动作用及其对MDPV诱导的机能亢进的作用。一系列体外结合和功能测定的结果证实，L-SPD充当D1样受体激动剂和D2样受体拮抗剂。在行为实验中，IVSA模型中L-SPD剂量依赖性地减弱了提示并加上MDPV引发的MDPV寻求行为的恢复。L-SPD的最高剂量也减弱了MDPV引发的MDPV CPP恢复，以及提示诱导的蔗糖恢复。L-SPD没有明显的运动作用，也没有调节由MDPV诱导的强健的机能亢进。目前的发现首次显示了MDPV的强大恢复作用，而L-SPD可以降低这种恢复作用。