Department of Psychology and CIAIMBITAL, CeiA3, University of Almería, Carretera de Sacramento s/n, 04120, Almería, Spain.
Psychopharmacology (Berl). 2018 Feb;235(2):419-432. doi: 10.1007/s00213-017-4819-y. Epub 2018 Jan 8.
Clinical studies have shown that some psychoactive recreational drugs have therapeutic applications in anxiety, depression, and schizophrenia. However, to date, there are few studies on the therapeutic potential efficacy of recreational drugs in compulsive neuropsychiatric disorders.
We explored the therapeutic potential of different psychoactive and psychedelic drugs in a preclinical model of compulsive behavior.
Outbred male Wistar rats were selected as either high (HD) or low (LD) drinkers according to their behavior in schedule-induced polydipsia (SIP). Subsequently, we assessed the effects of acute administration of scopolamine (0.125, 0.25, and 0.5 mg/kg), methamphetamine (0.25, 0.5, 1.25, and 2.5 mg/kg), ketamine (1.25, 2.5, 5, and 10 mg/kg), cannabidiol (1 and 3 mg/kg), WIN21255-2 (0.5, 075, and 1 mg/kg), and AM404 (0.25 and 0.5 mg/kg) on compulsive drinking in SIP.
Scopolamine reduced dose-dependent compulsive drinking in HD compared with LD rats in SIP. Methamphetamine induced a dose-dependent inverted U-curve effect in both groups, in which lower doses increased and higher doses reduced compulsive drinking in SIP. Ketamine, cannabidiol, WIN21255-2, and AM404 did not have any relevant effects in SIP.
These data provide new evidence that low doses of scopolamine and intermediate doses of methamphetamine might therapeutically reduce compulsive behaviors and suggest that there is not a direct participation of the endocannabinoid system in compulsive behavior on SIP. The research in the underlying neurochemical mechanisms of these psychoactive drugs might provide an additional insight on new therapeutic targets in compulsive neuropsychiatric disorders.
临床研究表明，一些具有致幻作用的娱乐性药物在焦虑、抑郁和精神分裂症方面具有治疗应用。然而，迄今为止，关于娱乐性药物在强迫性神经精神障碍中的治疗潜力的研究甚少。
我们在强迫行为的临床前模型中探索了不同致幻和迷幻药物的治疗潜力。
根据其在条件性饮水（SIP）中的行为，选择杂合雄性 Wistar 大鼠作为高（HD）或低（LD）饮水者。随后，我们评估了莨菪碱（0.125、0.25 和 0.5mg/kg）、甲基苯丙胺（0.25、0.5、1.25 和 2.5mg/kg）、氯胺酮（1.25、2.5、5 和 10mg/kg）、大麻二酚（1 和 3mg/kg）、WIN21255-2（0.5、0.75 和 1mg/kg）和 AM404（0.25 和 0.5mg/kg）对 SIP 中强迫性饮水的急性给药作用。
与 LD 大鼠相比，低剂量的莨菪碱降低了 HD 大鼠在 SIP 中的强迫性饮水。甲基苯丙胺在两组中均诱导了剂量依赖性的倒 U 型曲线效应，其中较低剂量增加，较高剂量减少 SIP 中的强迫性饮水。氯胺酮、大麻二酚、WIN21255-2 和 AM404 对 SIP 均无明显作用。
这些数据提供了新的证据，表明低剂量的莨菪碱和中等剂量的甲基苯丙胺可能在治疗上减少强迫行为，并表明内源性大麻素系统在 SIP 中的强迫行为中没有直接参与。对这些致幻药物的潜在神经化学机制的研究可能为强迫性神经精神障碍的新治疗靶点提供更多的见解。
