Cocaine Effects Are Modulated By Central Cb 2 Receptors In Mice: New Hope In A Cannabinoid Target For Addiction and Other Cns Disorders

Abstract

Evaluation of: Xi ZX, Peng XQ, Li X et al. Brain cannabinoid CB2receptors modulate cocaine’s actions in mice. Nat. Neurosci. 14(9), 1160–1166 (2011). This study aimed to investigate the possible involvement of brain CB2receptors in cocaine’s behavioral and neurochemical effects by using highly selective CB2receptor agonists and antagonists, combined with CB1and CB2receptor knockout mice. They found that systemic or intracerebral administration of the CB2selective agonist, JWH133, dose-dependently inhibited intravenous cocaine self-administration, cocaine-induced locomotion and cocaine-induced nucleus accumbens extracellular dopamine in wild-type and CB1receptor knockout mice, but not in CB2receptor knockout mice. These findings indicate that brain CB2receptors modulate cocaine’s reinforcing and locomotor-stimulating effects, likely through a dopamine-dependent mechanism, and further suggest that selective ligands targeting brain CB2receptors may represent a novel target for cocaine and other drug addictions as well as other CNS disorders.