Cocaine effects are modulated by central CB ₂ receptors in mice: New hope in a cannabinoid target for addiction and other CNS disorders

Evaluation of: Xi ZX, Peng XQ, Li X et al. Brain cannabinoid CB ₂ receptors modulate cocaines actions in mice. Nat. Neurosci. 14(9), 1160-1166 (2011). This study aimed to investigate the possible involvement of brain CB ₂ receptors in cocaines behavioral and neurochemical effects by using highly selective CB ₂ receptor agonists and antagonists, combined with CB ₁ and CB ₂ receptor knockout mice. They found that systemic or intracerebral administration of the CB ₂ selective agonist, JWH133, dose-dependently inhibited intravenous cocaine self-administration, cocaine-induced locomotion and cocaine-induced nucleus accumbens extracellular dopamine in wild-type and CB ₁ receptor knockout mice, but not in CB ₂ receptor knockout mice. These findings indicate that brain CB ₂ receptors modulate cocaines reinforcing and locomotor-stimulating effects, likely through a dopamine-dependent mechanism, and further suggest that selective ligands targeting brain CB ₂ receptors may represent a novel target for cocaine and other drug addictions as well as other CNS disorders.