Cannabinoid type-1 receptor signaling in central serotonergic neurons regulates anxiety-like behavior and sociability.

The endocannabinoid (eCB) system possesses neuromodulatory functions by influencing the release of various neurotransmitters, including γ-aminobutyric acid (GABA) and glutamate. A functional interaction between eCBs and the serotonergic system has already been suggested. Previously, we showed that cannabinoid type-1 (CB1) receptor mRNA and protein are localized in serotonergic neurons of the raphe nuclei, implying that the eCB system can modulate serotonergic functions. In order to substantiate the physiological role of the CB1 receptor in serotonergic neurons of the raphe nuclei, we generated serotonergic 5-hydroxytryptamine (5-HT) neuron-specific CB 1 receptor-deficient mice, using the Cr…