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



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.


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 (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.


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.


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


Psychostimulants Reward Drug abuse Addiction Memory Endocannabinoids 


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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