Attenuation of Cocaine-Induced Conditioned Place Preference and Motor Activity via Cannabinoid CB2 Receptor Agonism and CB1 Receptor Antagonism in Rats

Abstract

Background:Studies have shown the involvement of cannabinoid (CB) receptors in the behavioral and neurobiological effects of psychostimulants. Most of these studies have focused on the role of CB1 receptors in the psychostimulant effects of cocaine, while very few have investigated the respective role of CB2 receptors. Further studies are warranted to elucidate the extent of CB receptor involvement in the expression of cocaine-induced effects.Methods:The role of CB1 and CB2 receptors in the rewarding and motor properties of cocaine was assessed in conditioned place preference, conditioned motor activity, and open field activity in rats.Results:The CB1 receptor antagonist rimonabant (3 mg/kg) decreased the acquisition and the expression of conditioned place preference induced by cocaine (20 mg/kg). Rimonabant inhibited cocaine-elicited conditioned motor activity when administered during the expression of cocaine-induced conditioned place preference. Rimonabant decreased ambulatory and vertical activity induced by cocaine. The CB2 receptor agonist JWH-133 (10 mg/kg) decreased the acquisition and the expression of cocaine-induced conditioned place preference. JWH-133 inhibited cocaine-elicited conditioned motor activity when administered during the acquisition and the expression of cocaine-induced conditioned place preference. JWH-133 decreased ambulatory activity and abolished vertical activity induced by cocaine. The effects of JWH-133 on cocaine conditioned and stimulated responses were abolished when the CB2 receptor antagonist/inverse agonist AM630 (5 mg/kg) was preadministered.Conclusions:Cannabinoid CB1 and CB2 receptors modulate cocaine-induced rewarding behavior and appear to have opposite roles in the regulation of cocaine’s reinforcing and psychomotor effects.

Cannabinoid CB1 and CB2 receptor mechanisms underlie cannabis reward and aversion in rats

“…Similarly, overexpression of CB 2 receptors in the brain inhibits cocaine self‐administration and attenuates cocaine‐induced locomotor sensitization (Aracil‐Fernandez et al, ). Consistent with these findings, several recent reports indicate that CB 1 receptors and CB 2 receptors may play opposing roles in modulating cocaine's action, e.g., CB 2 receptor agonism exerting behavioural effects similar to those of CB 1 receptor antagonism on acquisition and expression of cocaine‐induced conditioned place preference, cocaine‐induced locomotion, cocaine‐induced c‐Fos expression and MAPK expression (Delis et al, ; Garcia‐Cabrerizo & Garcia‐Fuster, ). Such differential CB 1 versus CB 2 receptor effects may also partially explain some of the difficulty in parsing the neurological effects of cannabis use (Filbey et al, ).…”

Δ8‐Tetrahydrocannabivarin has potent anti‐nicotine effects in several rodent models of nicotine dependence

“…Recent published studies indicate that CB 2 receptor agonism produces potent anti‐addictive effects not dissimilar to those seen with CB 1 receptor antagonism (Jordan & Xi, ; Manzanares et al, ). As noted above, activation of CB 2 receptors by JWH133 inhibits cocaine self‐administration (Xi et al, ; Zhang et al, ; but see Adamczyk et al, ), cocaine‐induced CPP (Canseco‐Alba et al, ; Delis et al, ; Ignatowska‐Jankowska, Muldoon, Lichtman, & Damaj, ), and cocaine‐enhanced nucleus accumbens dopamine and locomotion in rodents (Delis et al, ; Xi et al, ). In contrast to these findings with cocaine, genetic deletion or pharmacological blockade (by AM630 or SR144528) of CB 2 receptors has been reported to attenuate nicotine‐induced CPP (Canseco‐Alba et al, ; Ignatowska‐Jankowska et al, ; Navarrete et al, ), nicotine self‐administration (Navarrete et al, ), and nicotine withdrawal symptoms (Navarrete et al, ; but see Ignatowska‐Jankowska et al, ).…”

“…CB 1 receptor antagonists have anti‐addiction efficacy in animal models, against a broad range of addictive substances (Cohen, Kodas, & Griebel, ; De Vries et al, ; Lupica, Riegel, & Hoffman, ; Maldonado et al, ; Tanda & Goldberg, ; Xi et al, ; Xi et al, ). CB 2 agonists have similar anti‐addiction efficacy in animal models (Delis et al, ; Jordan & Xi, ; Manzanares et al, ; Navarrete, García‐Gutiérrez, & Manzanares, ; Xi et al, ; Zhang et al, ).…”

Cannabidiol inhibits sucrose self‐administration by CB1 and CB2 receptor mechanisms in rodents

“…We previously reported that stimulation of VTA or NAc CB2Rs inhibits neuronal firing of DA neurons and decreases DA release in the NAc . Stimulation of CB2Rs by JWH133 inhibits cocaine self‐administration, cocaine‐induced locomotor hyperactivity and CPP, and electrical brain stimulation reward . Correspondingly, deletion of CB2Rs leads to enhanced CPP or locomotor response to cocaine or ethanol in mice, while overexpression of CB2Rs decreases cocaine sensitization and cocaine self‐administration .…”