Cannabinoids Elicit Antidepressant-Like Behavior and Activate Serotonergic Neurons through the Medial Prefrontal Cortex
Journal of Neuroscience October 24, 2007 Francis Rodriguez Bambico, Noam Katz, Guy Debonnel et al. 325 citations
Low doses of the cannabinoid CB1 receptor agonist WIN55,212-2 produce antidepressant-like effects in rats, as measured by the forced-swim test. This effect depends on CB1 receptors and the serotonin system, as it is blocked by the CB1 antagonist rimonabant and by serotonin depletion. Electrophysiology shows that low doses of WIN55,212-2 increase serotonin neuron firing in the dorsal raphe nucleus via a CB1-dependent mechanism, while high doses decrease firing through a CB1-independent mechanism and lack antidepressant effects. The enhancement of serotonin activity requires the ventromedial prefrontal cortex, as local microinjection there mimics the antidepressant effect, whereas lateral prefrontal cortex involvement is not needed.