CB1 receptor signaling at the cingulate-striatal circuit is anxiogenic

Abstract Cannabinoids, such as Δ9-tetrahydrocannabinol (THC), produce anxiety at high doses, yet the underlying neural mechanisms remain poorly understood. The anterior cingulate cortex (ACC) sends dense monosynaptic projections to the dorsomedial striatum (DMS). Optogenetic excitation of the ACC → DMS pathway promotes anxiolytic-like behavior, suggesting that its suppression could induce anxiogenic states. We hypothesized that CB1 receptor-mediated suppression of this circuit contributes to cannabinoid-induced anxiogenic effects. We found that endocannabinoid (eCB) system components are expressed in ACC → DMS neurons