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

• Published in: Psychopharmacology Vol. 237; no. 2; pp. 385 - 394
• Main Authors: Lopes, Jadna B., Bastos, Juliana R., Costa, Rayssa B., Aguiar, Daniele C., Moreira, Fabrício A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-02-2020; Springer; Springer Nature B.V
• Subjects: Addictions; Biomedical and Life Sciences; Biomedicine; c-Fos protein; Cannabinoid CB1 receptors; Cannabinoid CB2 receptors; Care and treatment; Cocaine; Dopamine; Endocannabinoid system; Enzymes; Hippocampus; Mesolimbic system; Neurons; Neurophysiology; Neurosciences; Neurotransmission; Original Investigation; Pharmacology/Toxicology; Place preference conditioning; Psychiatry; Substance abuse; Drug abuse; Reward; Addiction; Memory; Endocannabinoids; Psychostimulants
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-019-05370-5

Rationale
Cocaine is a psychostimulant drug that facilitates monoaminergic neurotransmission. The endocannabinoid system, comprising the cannabinoid receptors (CB
1
R and CB
2
R), 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 (CB
1
R antagonist; 0.3–10 mg/kg) or JWH133 (CB
2
R 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 (CB
2
R antagonist; 5 mg/kg). AM251 and JWH133 also prevented neuronal activation (c-Fos expression) in the hippocampus of CPP-exposed animals.
Conclusions
CB
1
R and CB
2
R have opposite roles in modulating cocaine-induced sensitization and CPP, possibly by preventing neuronal activation in the hippocampus.