Expression of functional cannabinoid CB₂ receptor in VTA dopamine neurons in rats

We have recently reported the expression of functional cannabinoid CB₂ receptors (CB₂Rs) in midbrain dopamine (DA) neurons in mice. However, little is known whether CB₂Rs are similarly expressed in rat brain because significant species differences in CB₂R structures and expression are found. In situ hybridization and immunohistochemical assays detected CB₂ gene and receptors in DA neurons of the ventral tegmental area (VTA), which was up-regulated in cocaine self-administration rats. Electrophysiological studies demonstrated that activation of CB₂Rs by JWH133 inhibited VTA DA neuronal firing in single dissociated neurons. Systemic administration of JWH133 failed to alter, while local administration of JWH133 into the nucleus accumbens inhibited cocaine-enhanced extracellular DA and i.v. cocaine self-administration. This effect was blocked by AM630, a selective CB₂R antagonist. These data suggest that CB₂Rs are expressed in VTA DA neurons and functionally modulate DA neuronal activities and cocaine self-administration behavior in rats.