Centre for Drug Research, Universiti Sains Malaysia, 11800 Gelugor, Penang, Malaysia.
Centre for Drug Research, Universiti Sains Malaysia, 11800 Gelugor, Penang, Malaysia.
Behav Brain Res. 2023 Sep 13;453:114638. doi: 10.1016/j.bbr.2023.114638. Epub 2023 Aug 22.
Mitragynine (MG) is the primary active constituent of Mitragyna speciosa Korth (kratom), a psychoactive Southeast Asian plant with potential therapeutic use. Numerous studies support roles of dopaminergic system in drug reward. However, the involvement of the dopaminergic system in mediating MG reward and drug-seeking is poorly understood. Using conditioned place preference (CPP) paradigm, the present study aims to evaluate the roles of the dopamine (DA) D1 receptor in the acquisition and expression of MG-induced CPP in rats. The effects of SCH-23390, a selective DA D1 receptor antagonist, on the acquisition of MG-induced CPP were first investigated. Rats were pre-treated systemically with SCH-23390 (0, 0.1 and 0.3 mg/kg, i.p.) prior to MG (10 mg/kg) conditioning sessions. Next, we tested the effects of the DA D1 receptor antagonist on the expression of MG-induced CPP. Furthermore, the effects of a MG-priming dose (5 mg/kg) on the reinstatement of extinguished CPP were tested. The results showed that SCH-23390 dose-dependently suppressed the acquisition of a MG-induced CPP. In contrast, SCH-23390 had no effect on the expression of a MG-induced CPP. The findings of this study suggested a crucial role of the DA D1 receptor in the acquisition, but not the expression of the rewarding effects of MG in a CPP test. Furthermore, blockade of the D1-like receptor during conditioning did not prevent MG priming effects on CPP reinstatement test, suggesting no role for the DA D1 receptor in reinstatement sensitivity.
美托拉宗（MG）是美托拉诺树（Kratom）的主要活性成分，美托拉诺树是一种具有潜在治疗作用的东南亚精神活性植物。大量研究支持多巴胺能系统在药物奖赏中的作用。然而，多巴胺能系统在介导 MG 奖赏和觅药行为中的作用仍知之甚少。本研究采用条件位置偏好（CPP）范式，旨在评估多巴胺（DA）D1 受体在 MG 诱导的 CPP 在大鼠中的获得和表达中的作用。首先研究了选择性 DA D1 受体拮抗剂 SCH-23390 对 MG 诱导的 CPP 获得的影响。大鼠在 MG（10mg/kg）条件作用前，分别给予 SCH-23390（0、0.1 和 0.3mg/kg，ip）预处理。接下来，我们测试了 DA D1 受体拮抗剂对 MG 诱导的 CPP 表达的影响。此外，还测试了 MG 引发剂量（5mg/kg）对消退的 CPP 复燃的影响。结果表明，SCH-23390 呈剂量依赖性地抑制 MG 诱导的 CPP 的获得。相反，SCH-23390 对 MG 诱导的 CPP 的表达没有影响。这项研究的结果表明，DA D1 受体在 CPP 测试中对 MG 奖赏效应的获得具有重要作用，但对表达没有作用。此外，在条件作用期间阻断 D1 样受体并不能防止 MG 引发对 CPP 复燃测试的影响，表明 DA D1 受体在复燃敏感性中不起作用。
