Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos 6627, Belo Horizonte, MG, 31270-901, Brazil.
Psychopharmacology (Berl). 2020 Feb;237(2):385-394. doi: 10.1007/s00213-019-05370-5. Epub 2019 Oct 30.
Cocaine is a psychostimulant drug that facilitates monoaminergic neurotransmission. The endocannabinoid system, comprising the cannabinoid receptors (CBR and CBR), the endocannabinoids, and their metabolizing-enzymes, modulates the mesolimbic dopaminergic pathway and represents a potential target for the treatment of addiction.
Here, we tested the hypothesis that the cannabinoid receptors are implicated in cocaine-induced motor sensitization, conditioned place preference (CPP), and hippocampal activation.
Male Swiss mice received injections of AM251 (CBR antagonist; 0.3-10 mg/kg) or JWH133 (CBR agonist; 1-10 mg/kg) before acquisition or expression of cocaine (20 mg/kg)-induced sensitization and CPP. After the CPP test, cFos-staining was employed as a marker of neuronal activation in the hippocampus.
AM251 inhibited the acquisition (0.3, 1, and 3 mg/kg) and expression (1 and 3 mg/kg) of sensitization, as well as the acquisition (10 mg/kg) of CPP. JWH133 inhibited the acquisition (0.3 and 1 mg/kg) and expression (1 and 3 mg/kg) of both sensitization and CPP. JWH133 effects were reversed by AM630 (CBR antagonist; 5 mg/kg). AM251 and JWH133 also prevented neuronal activation (c-Fos expression) in the hippocampus of CPP-exposed animals.
CBR and CBR have opposite roles in modulating cocaine-induced sensitization and CPP, possibly by preventing neuronal activation in the hippocampus.
可卡因是一种促进单胺能神经传递的精神兴奋剂。内源性大麻素系统由大麻素受体（CBR 和 CBR）、内源性大麻素及其代谢酶组成，调节中脑边缘多巴胺能通路，代表了治疗成瘾的潜在靶点。
在这里，我们检验了这样一个假设，即大麻素受体参与了可卡因诱导的运动敏化、条件性位置偏爱（CPP）和海马激活。
雄性瑞士小鼠在可卡因（20mg/kg）诱导的敏化和 CPP 的获得或表达之前接受 AM251（CBR 拮抗剂；0.3-10mg/kg）或 JWH133（CBR 激动剂；1-10mg/kg）的注射。在 CPP 测试后，使用 cFos 染色作为海马神经元激活的标志物。
AM251 抑制了敏化的获得（0.3、1 和 3mg/kg）和表达（1 和 3mg/kg），以及 CPP 的获得（10mg/kg）。JWH133 抑制了敏化和 CPP 的获得（0.3 和 1mg/kg）和表达（1 和 3mg/kg）。JWH133 的作用被 AM630（CBR 拮抗剂；5mg/kg）逆转。AM251 和 JWH133 还防止了 CPP 暴露动物海马神经元的激活（c-Fos 表达）。
CBR 和 CBR 在调节可卡因诱导的敏化和 CPP 方面具有相反的作用，可能通过防止海马神经元的激活来实现。
