大麻素 CB1 和 CB2 受体在可卡因诱导的行为敏化和条件性位置偏爱中的作用。

The roles of cannabinoid CB1 and CB2 receptors in cocaine-induced behavioral sensitization and conditioned place preference in mice.

机构信息

Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos 6627, Belo Horizonte, MG, 31270-901, Brazil.

出版信息

Psychopharmacology (Berl). 2020 Feb;237(2):385-394. doi: 10.1007/s00213-019-05370-5. Epub 2019 Oct 30.

DOI:10.1007/s00213-019-05370-5

PMID:31667531

Abstract

RATIONALE

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.

OBJECTIVES

Here, we tested the hypothesis that the cannabinoid receptors are implicated in cocaine-induced motor sensitization, conditioned place preference (CPP), and hippocampal activation.

METHODS

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.

RESULTS

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.

CONCLUSIONS

CBR and CBR have opposite roles in modulating cocaine-induced sensitization and CPP, possibly by preventing neuronal activation in the hippocampus.

摘要

原理

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。

目的

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。

方法

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。

结果

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）。