Optogenetic brain‐stimulation reward: A new procedure to re‐evaluate the rewarding versus aversive effects of cannabinoids in dopamine transporter‐Cre mice
Addiction Biology February 3, 2021 Bree A. Humburg, Chloe J. Jordan, Hai‐Ying Zhang et al. 30 citations
Most cannabinoids reduce rather than enhance reward-seeking behavior in mice, according to an optogenetic self-stimulation procedure. Cocaine dose-dependently increased responding, shifting stimulation–response curves upward. In contrast, Δ9-tetrahydrocannabinol (THC), WIN55,212-2, and ACEA dose-dependently decreased responding and shifted curves downward; cannabidiol had no effect. Among newer synthetic cannabinoids, XLR-11 produced a cocaine-like increase, AM-2201 produced a THC-like reduction, and 5F-AMB had no effect. CB1 receptors were expressed mainly in VTA GABA and glutamate neurons, while CB2 receptors were expressed mainly in VTA dopamine neurons. These findings suggest most cannabinoids are reward attenuating or aversive in mice.