Röpke Jivago, Busanello Alcindo, Leal Caroline Queiroz, de Moraes Reis Elizete, de Freitas Catiuscia Molz, Villarinho Jardel Gomes, Figueira Fernanda Hernandes, Mello Carlos Fernando, Ferreira Juliano, Fachinetto Roselei
Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, RS, Brazil.
Curso de Farmácia, Universidade Federal de Santa Maria, RS, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2014 Oct 3;54:195-9. doi: 10.1016/j.pnpbp.2014.04.006. Epub 2014 Apr 18.
Antipsychotics may cause tardive dyskinesia in humans and orofacial dyskinesia in rodents. Although the dopaminergic system has been implicated in these movement disorders, which involve the basal ganglia, their underlying pathomechanisms remain unclear. CB1 cannabinoid receptors are highly expressed in the basal ganglia, and a potential role for endocannabinoids in the control of basal ganglia-related movement disorders has been proposed. Therefore, this study investigated whether CB1 receptors are involved in haloperidol-induced orofacial dyskinesia in rats. Adult male rats were treated for four weeks with haloperidol decanoate (38mg/kg, intramuscularly - i.m.). The effect of anandamide (6nmol, intracerebroventricularly - i.c.v.) and/or the CB1 receptor antagonist SR141716A (30μg, i.c.v.) on haloperidol-induced vacuous chewing movements (VCMs) was assessed 28days after the start of the haloperidol treatment. Anandamide reversed haloperidol-induced VCMs; SR141716A (30μg, i.c.v.) did not alter haloperidol-induced VCM per se but prevented the effect of anandamide on VCM in rats. These results suggest that CB1 receptors may prevent haloperidol-induced VCMs in rats, implicating CB1 receptor-mediated cannabinoid signaling in orofacial dyskinesia.
抗精神病药物可能会导致人类出现迟发性运动障碍，在啮齿动物中则会引发口面部运动障碍。尽管多巴胺能系统与这些涉及基底神经节的运动障碍有关，但其潜在的发病机制仍不清楚。CB1大麻素受体在基底神经节中高度表达，并且有人提出内源性大麻素在控制基底神经节相关运动障碍中可能发挥作用。因此，本研究调查了CB1受体是否参与氟哌啶醇诱导的大鼠口面部运动障碍。成年雄性大鼠用癸酸氟哌啶醇（38mg/kg, 肌肉注射）治疗四周。在氟哌啶醇治疗开始28天后评估花生四烯乙醇胺（6nmol, 脑室内注射）和/或CB1受体拮抗剂SR141716A（30μg, 脑室内注射）对氟哌啶醇诱导的空嚼运动（VCMs）的影响。花生四烯乙醇胺可逆转氟哌啶醇诱导的VCMs；SR141716A（30μg,脑室内注射）本身不会改变氟哌啶醇诱导的VCMs，但可阻止花生四烯乙醇胺对大鼠VCMs的影响。这些结果表明，CB1受体可能会预防氟哌啶醇诱导的大鼠VCMs，这意味着CB1受体介导的大麻素信号传导与口面部运动障碍有关。
