Efeitos de fármacos que atuam no sistema canabinoide sobre a modulação dos comportamentos defensivos avaliados no labirinto em T elevado

Abstract

Anxiety is an adapting emotion related to defensive responses. It may, however, occur excessively, characterizing psychiatric disorders, such as panic and generalized anxiety disorders, which are the focus of this work. Studies with experimental animals have been important to better characterize and elucidate their neurobiology and pharmacology. Hence, the importance of animal models to evaluate each specific disorder. In this context the elevated T maze (LTE) has been developed to evaluate two distinct tasks in the same animal: inhibitory avoidance, related to generalized anxiety disorder, and the escape response, predictive of panic disorder. Several neurotransmitters may modulate such behaviors, including the endocannabinoid system. Previous studies have demonstrated that both agonists and antagonists of cannabinoid receptors can yield complex responses in standard models of anxiety. Based on this evidence, the purpose of this study was to test the hypothesis that drugs that facilitate the endocannabinoid system would induce anxiolytic and anti-panic effects in the LTE. Treatment with the cannabinoid agonist WIN 55-212 (1,0 mg/Kg) decreased the latency to leave the enclosed arm in the inhibitory avoidance task, characterizing an anxiolytic-like effect, which could be prevented by pretreatment with the CB1 receptor antagonist AM 251 (1,0mg/Kg). At the higher dose (3,0 mg/Kg) this antagonist also promoted anxiogenic-like effect, however a similar behavior was not observed with rimonabant (3.0 mg/Kg), another antagonist. None of these drugs changed escape task. The inhibitor of anandamide hydrolysis, URB597 (0,3 and 1,0 mg/kg) reduced the latency to the leave the enclosed arm, and increased the latency to get out of open arm, typical of anxiolytic and panicolytic effects, respectively. Together, these results suggest that drugs that act on the cannabinoid system have different effects in the behaviors assessed in LTE.