CB2 agonist mitigates cocaine-induced reinstatement of place preference and modulates the inflammatory response in mice

Author:

Abboussi Oualid1,Khan Zmarak Ahmad2,Ibork Hind1,Zulu Simo S.3,Daniels William4,Taghzouti Khalid1,Hales Tim G.2

Affiliation:

1. Physiology and Physiopathology Team, Faculty of Sciences, Genomic of Human Pathologies Research Centre, Mohammed V University in Rabat, Rabat, Morocco

2. Institute of Academic Anaesthesia, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK

3. Department of Human Biology, Faculty of Health Sciences, Nelson Mandela University, Port Elisabeth

4. School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Abstract

Chronic exposure to cocaine is known to have profound effects on the brain, leading to the dysregulation of inflammatory signalling pathways, the activation of microglia, and the manifestation of cognitive and motivational behavioural impairments. The endocannabinoid system has emerged as a potential mediator of cocaine’s deleterious effects. In this study, we sought to investigate the therapeutic potential of the cannabinoid CB2 receptor agonist, JWH-133, in mitigating cocaine-induced inflammation and associated motivational behavioural alterations in an in vivo model. Our research uncovered compelling evidence that JWH-133, a selective CB2 receptor agonist, exerts a significant dampening effect on the reinstatement of cocaine-induced conditioned place preference. This effect was accompanied by notable changes in the neurobiological landscape. Specifically, JWH-133 administration was found to upregulate Δ-FOSB expression in the nucleus accumbens (Nac), elevate CX3CL1 levels in both the ventral tegmental area and prefrontal cortex (PFC), and concurrently reduce IL-1β expression in the PFC and NAc among cocaine-treated animals. These findings highlight the modulatory role of CB2 cannabinoid receptor activation in altering the reward-seeking behaviour induced by cocaine. Moreover, they shed light on the intricate interplay between the endocannabinoid system and cocaine-induced neurobiological changes, paving the way for potential therapeutic interventions targeting CB2 receptors in the context of cocaine addiction and associated behavioural deficits.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Psychiatry and Mental health,Pharmacology

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