Cannabinoid CB1 receptors mediate the anxiolytic effects induced by systemic alprazolam and intra-periaqueductal gray 5-HT1A receptor activation

The endocannabinoid system has been implicated in the modulation of behaviors related to anxiety and panic disorders. Accordingly, facilitation of CBI receptor signaling reduces the consequences of aversive stimuli in animal models. However, the role of the CBI receptor in the effects of anxiolytic drugs has remained unclear. Here, we tested the hypothesis that the anxiolytic and panicolytic responses to systemic alprazolam injection and local 5-HT1A receptor activation in the dorsolateral periaqueductal gray (dlPAG) depend on CB1 receptor activation. Systemic injection of alprazolam (4 mg/kg) induced an anxiolytic-like effect in the elevated T maze (ETM) model of panic and anxiety, which was prevented by the CB1 antagonist AM251 (0.3 mg/kg). Likewise, intra-dlPAG injection of the 5-HT1A receptor agonist 8-OH-DPAT (3.2 nmol/0.2 u L) also reduced anxiety-like behavior, a response prevented by intra-dlPAG injection of AM251 (100 pmol/0.2 mu L). 8-OH-DPAT (8 nmol/0.2 mu L) also presented a panicolytic-like activity in the escape reaction induced by chemical stimulation of the dlPAG, which was not prevented by AM251 (100 pmol/0.2 mu L). These results suggest that CB1 receptor signaling is involved in the effects of anxiolytic drugs, with potential implications for developing new treatments for anxiety disorders.