THE FATTY ACID AMIDE HYDROLASE ENZYME INHIBITION IN GLOBUS PALLIDUS CAUSES PANICOLYTIC LIKE EFFECT IN PREY THREATNED BY BOTHROPS JARARACA

Abstract The endocannabinoid modulation of fear and anxiety due to their on-demand synthesis and degradation is supported by a large body of research. Although it has been proposed that the anandamide (AEA) in the globus pallidus (GP) seems to be important for the modulation of innate fear-related behaviours, a role for endogenous AEA has yet to be clarified. Rats were treated with the fatty acid amide hydrolase (FAAH) selective inhibitor URB597 at different concentrations (0.01, 0.1, 1 nmol/ 0.1 µL) in the GP followed by bicuculline microinjections in dlSC and confronted by a lancehead pit viper (Bothrops jararaca) in the enriched polygonal arena for snake panic test. The most effective dose of URB597 (1 nmol) was also preceded by microinjections of the CB1 receptor antagonist AM251 (0.1 nmol) in the GP, and rats were then confronted by venomous snakes. URB597 (0.1 and 1 nmol) in the GP decreased the expression of defensive behaviours such as defensive attention, escape, and time spent inside the burrow of animals confronted by pit vipers. Moreover, the pretreatment of the GP with AM251 suppressed these antiaversive effects of URB597 in such midbrain structure. Overall, these data clearly indicate that the panicolytic consequences of the endogenous AEA enhancement in the GP are mediated by CB1 receptors signalling.