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

  • Jadna B. Lopes
  • Juliana R. Bastos
  • Rayssa B. Costa
  • Daniele C. Aguiar
  • Fabrício A. MoreiraEmail author
Original Investigation

Abstract

Rationale

Cocaine is a psychostimulant drug that facilitates monoaminergic neurotransmission. The endocannabinoid system, comprising the cannabinoid receptors (CB1R and CB2R), 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 (CB1R antagonist; 0.3–10 mg/kg) or JWH133 (CB2R 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 (CB2R antagonist; 5 mg/kg). AM251 and JWH133 also prevented neuronal activation (c-Fos expression) in the hippocampus of CPP-exposed animals.

Conclusions

CB1R and CB2R have opposite roles in modulating cocaine-induced sensitization and CPP, possibly by preventing neuronal activation in the hippocampus.

Keywords

Psychostimulants Reward Drug abuse Addiction Memory Endocannabinoids 

Notes

Funding information

This research was funded by Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG; APQ-02064-15), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; 406122/2016-4) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; 2017/24304-0).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmacology, Institute of Biological SciencesUniversidade Federal de Minas GeraisBelo HorizonteBrazil

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