Wuhan Institutes of Biomedical Sciences, Jianghan University, Wuhan 430056, China.
Pharmacol Biochem Behav. 2012 Jul;102(1):1-5. doi: 10.1016/j.pbb.2012.03.014. Epub 2012 Mar 27.
Opiate addiction is a chronic recrudescent disorder characterized by a high rate of relapse. Levo-tetrahydropalmatine (l-THP) is an alkaloid substance extracted from Corydalis and Stephania and is contained in a number of traditional Chinese herbal preparations. Compared to other dopamine receptor antagonists, l-THP has lower affinity for D2 receptors than for D1 receptors, and a recent study showed that l-THP also binds to D3 receptors, possibly functioning as an antagonist. The unique pharmacological profile of l-THP suggests that l-THP may be effective for the treatment of opiate addiction. In this study, we investigated the effects of l-THP on heroin self-administration and reinstatement triggered by a priming injection of heroin in abstinent rats trained to stably self-administer heroin under an extinction/reinstatement protocol, and found that l-THP (2.5 and 5 mg/kg, i.p.) decreased heroin self-administration on the fixed-ratio 1 schedule and dose-dependently (1.25, 2.5 and 5 mg/kg, i.p.) inhibited heroin-induced reinstatement of heroin-seeking behavior. Importantly, l-THP (1.25 and 2.5 mg/kg, i.p.) did not affect locomotion, indicating that the observed effects of l-THP on reinstatement do not appear to be due to motor impairments. The present results demonstrated that dopamine receptor antagonist l-THP attenuates heroin self-administration and heroin-induced reinstatement.
阿片类药物成瘾是一种慢性复发性疾病，其特点是复发率高。左旋四氢巴马汀（l-THP）是从延胡索和千金藤中提取的一种生物碱物质，存在于许多中药制剂中。与其他多巴胺受体拮抗剂相比，l-THP 对 D2 受体的亲和力低于 D1 受体，最近的一项研究表明，l-THP 还与 D3 受体结合，可能作为拮抗剂发挥作用。l-THP 的独特药理学特性表明，l-THP 可能对治疗阿片类药物成瘾有效。在这项研究中，我们研究了 l-THP 对海洛因自我给药和海洛因引发的复吸的影响，在已稳定接受海洛因自我给药的大鼠中，使用海洛因引发复吸的方案进行训练，我们发现 l-THP（2.5 和 5 mg/kg，ip）减少了固定比率 1 方案下的海洛因自我给药，且呈剂量依赖性（1.25、2.5 和 5 mg/kg，ip）抑制了海洛因引发的觅药行为复吸。重要的是，l-THP（1.25 和 2.5 mg/kg，ip）并不影响运动，这表明 l-THP 对复吸的观察到的影响似乎不是由于运动障碍引起的。本研究结果表明，多巴胺受体拮抗剂 l-THP 可减弱海洛因自我给药和海洛因诱导的复吸。
