Efeitos de drogas que atuam no sistema endocanabinoide injetadas na substância cinzenta periaquedutal dorsolateral na modulação de comportamentos defensivos

Abstract

Rodents present a repertoire of defensive behaviours to aversive situations. An important encephalic region involved in the expression of these behaviours is the dorsolateral periaqueductal gray matter (dlPAG). In humans, stimulation of this region causes a reaction similar to a panic attack. In rats, it causes escape reactions that can be interpreted as a panic-like response. In this same region, CB1 receptor activation induces anti-aversive effects. Considering these aspects, the objective of the present work was to test the hypothesis that CB1 receptor activation in the dlPAG attenuates the escape reaction. Dose-response curves were performed with the anandamide hydrolisis inhibitor, URB597 (vehicle n=7 n= 0,3 nmol n=9; 1 nmol n=8; 3 nmol n=8) and with the CB1 selective agonist, ACEA (vehicle n= 8; 0,005 pmol n=9; 0,05 pmol n=5 e 0,5 pmol n=5). ACEA (0,005 pmol and 0,5 pmol) had a panicolytic effect (two-way ANOVA with repeated measures). Concerning URB597, a discrete panicolytic effect was observed with the dose of 0,3nmol. URB597 was again tested as well as the pre-tretment with the AM251 antagonist. In this experiment, 0,3nmol of URB597 didnt change the escape reaction. URB597 was then tested in the escape reaction induced by DLH in the dlPAG, a model in wich, hypothetically, there is an augmented synthesis and release of anandamide relative to the ETM model. In this model, URB597 attenuated the escape reaction with the reduction of one of two parameters measured, the number of jumps in a box (P<0,05, Mann Whitney s test) (vehicle n=5; veículo- DLH=7; 0,3 nmol=7; 0,1 nmol=6; 0,1 nmol=6). It can be concluded that CB1 receptor activation and the anandamide hydrolisis inhibition induces panicolytic effect in the ETM and the escape reaction induced by DLH in the dlPAG models, respectively.