Dopamine D1 receptor antagonist reduces stimulant-induced conditioned place preferences and dopamine receptor supersensitivity
Dopamine D1 receptor antagonist reduces stimulant-induced conditioned place preferences and dopamine receptor supersensitivity
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DOI：
10.1007/s00210-019-01694-3
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发表时间：
2019-11-13
影响因子：
3.6
通讯作者：
Yun, Jaesuk
中科院分区：
文献类型：
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作者：
Gu, Sun Mi;Cha, Hye Jin;Yun, Jaesuk
反复给药可诱导条件性位置偏爱(CPP)。多巴胺受体超敏反应在兴奋剂诱导的CPP动物中发生；然而，与CPP动物超敏反应发展相关的多巴胺受体亚型在很大程度上是未知的。本临床前研究旨在探讨多巴胺D_1或D_2受体拮抗剂是否对兴奋剂诱导的心理行为产生抑制作用。此外，作者的目的是阐明多巴胺受体超敏在奖赏相关行为发展中的作用。分别用多巴胺D1(SCH23390)或舒必利(D2)受体拮抗剂对甲基安非他明和可卡因诱导的大鼠CPP进行治疗。CPP实验结束后，用阿朴吗啡(多巴胺受体激动剂)激发大鼠，测量其运动能力。SCH23390可降低甲基苯丙胺和可卡因诱导的CPP，但舒必利不能。此外，阿朴吗啡激发刺激预处理大鼠的运动活动增加，反映了多巴胺受体的超敏反应。SCH23390预处理可抑制多巴胺受体超敏反应的发展，舒必利则无抑制作用。这些结果提示，多巴胺D_1受体拮抗剂SCH23390可抑制多巴胺受体超敏反应的形成，这与CPP的发生有关。
Repeated administration of stimulants induces conditioned place preference (CPP). Dopamine receptor supersensitivity is developed in stimulant-induced CPP animals; however, dopamine receptor subtypes associated with the development of supersensitivity in CPP animals are largely unknown. The present preclinical study aimed to examine whether dopamine D1 or D2 receptor antagonists exert inhibitory effects on stimulant-induced psychological behaviors. Additionally, the authors aimed to elucidate the role of dopamine receptor supersensitivity on the development of reward-related behavior. Sprague Dawley rats subjected to methamphetamine- and cocaine-induced CPP tests were treated with dopamine D1 (SCH23390) or D2 (sulpiride) receptor antagonists. Following the CPP experiment, rats were challenged with apomorphine (dopamine receptor agonist), and locomotor activity was measured. Methamphetamine- and cocaine-induced CPP was reduced with the administration of SCH23390, but not sulpiride. In addition, the apomorphine challenge evoked an increase in locomotor activity in stimulant-pre-treated rats, reflecting dopamine receptor supersensitivity. SCH23390 pre-treatment inhibited the development of dopamine receptor supersensitivity, while sulpiride demonstrated no inhibitory effects. These results suggest that the dopamine D1 receptor antagonist SCH23390 inhibits the development of dopamine receptor supersensitivity which is associated with the development of CPP.