Cannabinoid-1 receptor gene deletion has a compartment-specific affect on the dendritic and axonal availability of μ-opioid receptors and on dopamine axons in the mouse nucleus accumbens

Cannabinoid-type 1 (CB1) receptors are implicated in μ-opioid receptor (μ-OR)-dependent reward ascribed partially to mesolimbic dopamine release in the nucleus accumbens (Acb) shell. Thus, CB1 receptor gene deletion may preferentially alter the availability of μ-ORs and/or dopamine innervation in this brain region, which is functionally distinct from the motor-associated Acb core. To test this hypothesis, we examined the electron microscopic immunolabeling of the μ-OR and the dopamine-synthesizing enzyme, tyrosine hydroxylase (TH) in Acb shell, and core of adult C57BL/6J wild-type (WT) and CB1-knock-out (KO) mice. The μ-OR-immunogold particles were observed in the cytoplasm and on the plasmalemma in dendrites, dendritic spines, and axon terminals throughout the Acb. Compared to WT, the Acb shell of CB1-KO mice showed a lower cytoplasmic density of μ-ORs in dendrites and fewer μ-OR labeled, but not unlabeled, dendritic spines. In this region, the CB1-KO's had a significantly enhanced plasmalemmal density of μ-OR-immunogold in axon terminals, 70% of which formed excitatory-type synapses. However, the number of both μ-OR-labeled terminals and TH-labeled small varicosities was significantly reduced in the Acb shell of CB1-KO's. These adaptations were not seen in the Acb core, where CB1-KO's had a preferentially lower dendritic plasmalemmal and total spine density of μ-OR immunogold. Our results indicate that constitutive deletion of the CB1 receptor gene has a major impact on the pre and postsynaptic availability of μ-ORs at axospinous synapses and on the dopamine innervation of the Acb shell as well as the dendritic surface expression of μ-ORs in Acb core of mature rodents.