Attenuation of basal and cocaine-enhanced locomotion and nucleus accumbens dopamine in cannabinoid CB1-receptor-knockout mice

Rationale  Effect of cannabinoid CB1 receptor deletion on cocaine’s actions is controversial. This is partly based on findings in CB1-receptor-knockout (CB1^−/−) mice with CD1 genetic background. Objectives  In the present study, we used CB1^−/− mice with a C57BL/6J genetic background to further investigate the role of CB1 receptors in cocaine’s action. Materials and methods  Locomotor activity was assessed using AccuScan locomotor chambers. Brain extracellular dopamine (DA) levels were measured by in vivo microdialysis and by fast-scan cyclic voltammetry in the nucleus accumbens (NAc). Results  CB1^−/− mice displayed a significant reduction in basal levels of locomotion and extracellular DA, as well as in cocaine-enhanced locomotion and extracellular DA, as compared to their wild-type (CB1^+/+) littermates. The reduction in basal and cocaine-enhanced DA appears to be related to a reduction in basal DA release, not to an increase in DA clearance, as indicated by fast-scan cyclic voltammetry in brain slices. Pharmacological blockade of CB1 receptors by SR141716 inhibited locomotion and NAc DA release in CB1^+/+ mice. Conclusions  The present findings suggest an important role for CB1 receptors in mediating cocaine’s behavioral and neurochemical effects.