Effects of compounds that interfere with the endocannabinoid system on behaviors predictive of anxiolytic and panicolytic activities in the elevated T-maze

An extensive literature has implicated the endocannabinoid system in the modulation anxiety-related responses. Nonetheless, it remains uncertain what would be the effects of endocannabinoid-related compounds against responses related to specific subtypes of anxiety disorders, particularly generalized anxiety and panic. In this context, the elevated T maze (ETM) has been developed to evaluate two distinct tasks in the same rat, inhibitory avoidance and escape response from an open arm, predictive of anxiolytic and panicolytic effects, respectively. Thus, the present study tested the hypothesis that drugs that facilitate endocannabinoid-signaling would inhibit both types of aversive responses in this model. As positive controls, diazepam attenuated only inhibitory avoidance (anxiolytic-like effect), whereas alprazolam was effective against both avoidance and escape (anxiolytic- and panicolytic like effects). The synthetic cannabinoid WIN55,212-2 (1.0 mg/kg) promoted an anxiolytic-like effect, which was prevented by pre-treatment with the CB1 receptor antagonist, AM 251 (1.0 mg/kg). At the higher dose (3.0 mg/kg), this antagonist promoted an anxiogenic-like effect. None of these drugs interfered with the escape task. The endocannabinoid (anandamide) hydrolysis inhibitor, URB 597 at doses of 0.3 and 1.0 mg/kg, induced, respectively, panicolytic- and anxiolytic-like effects, which were reversed by pretreatment with AM 251. These results suggest that drugs that act on the endocannabinoid system have different effects on the behaviors assessed in the ETM.