Cannabidiol attenuates the rewarding effects of cocaine in rats by CB2, 5-TH1A and TRPV1 receptor mechanisms.

Spread the love

Cocaine abuse continues to be a serious health problem worldwide. Despite intense research there is currently no FDA-approved medication to treat cocaine use disorder. The recent search has been focused on agents targeting primarily the dopamine system, while limited success has been achieved at the clinical level. Cannabidiol (CBD) is a U.S. FDA-approved cannabinoid for the treatment of epilepsy and recently was reported to have therapeutic potential for other disorders. Here we systemically evaluated its potential utility for the treatment of cocaine addiction and explored the underlying receptor mechanisms in experimental animals. Systemic administration (10-40 mg/kg) of CBD dose-dependently inhibited cocaine self-administration, shifted cocaine dose-response curve downward, and lowered break-point for cocaine self-administration under a progressive-ratio schedule of reinforcement. CBD inhibited cocaine self-administration maintained by low, but not high, doses of cocaine. In addition, CBD (3-20 mg/kg) dose-dependently attenuated cocaine-enhanced brain-stimulation reward (BSR) in rats. Strikingly, this reduction in both cocaine self-administration and BSR was blocked by AM630 (cannabinoid CB2 receptor antagonist), WAY100135 (5-HT1A receptor antagonist), or capsazepine (TRPV1 channel blocker), but not by AM251 (CB1 receptor antagonist), CID16020046 (GPR55 antagonist), or naloxone (opioid receptor antagonist), suggesting the involvement of CB2, 5-HT1A, and TRPV1 receptors in CBD action. In vivo microdialysis indicated that pretreatment with CBD (10-20 mg/kg) attenuated cocaine-induced increases in extracellular dopamine (DA) in the nucleus accumbens, while CBD alone failed to alter extracellular DA. These findings suggest that CBD may have certain therapeutic utility by blunting the acute rewarding effects of cocaine via a DA-dependent mechanism.

error: Content is protected !!
%d blogueurs aiment cette page :