Figure 11.

Effects of Δ⁹-THC on open-field locomotion and anxiety-like behavior. A–C, Systemic administration of Δ⁹-THC (1, 3, 10 mg/kg, i.p., 15 min prior to testing) dose-dependently inhibited open-field locomotion in CB1-flox mice, DAT-Cre mice, and DA-CB1-KO mice. D, Calculation of the area under curve (AUC) of locomotor activity indicates that DA-CB1-KO mice displayed a significantly higher basal level of locomotion (before Δ⁹-THC administration) than CB1-flox mice or DAT-Cre mice. E–G, Calculated AUC data indicating the dose-dependent locomotor effects of Δ⁹-THC in CB1-flox mice, DAT-Cre mice, and DA-CB1-KO mice. Deletion of CB1R from DA neurons blocked lower doses (3 mg/kg) of Δ⁹-THC-induced reduction in locomotion (G). H, An image of EPM device we used in this study. I, Δ⁹-THC, at low doses (0.3 mg/kg), produced anxiolytic effects, manifested as increased time in the open arms of the EPM device. Deletion of CB1R from DA neurons reversed Δ⁹-THC's anxiolytic effects, producing an opposite anxiogenic effect as assessed by decreased time spent in the open arms of the EPM device.