Ativação do receptor canabinóide tipo 1 (CB1r) previne o estresse oxidativo cerebral e inibe o comportamento tipo agressivo em Danio rerio (Zebrafish)

Abstract

Aggression is a set of complex actions that involve several factors of a genetic, neurophysiological, hormonal and behavioral nature. Furthermore, the brain redox state can also influence aggressive behavior in different species. Thus, modulators of this process can influence the expression of aggressive episodes, between them is the Endocannabinoid System that acts as the main neuromodulator of the CNS, in addition to exerting an antioxidant effect in different conditions. However, its participation in the modulation of aggressive-like behavior needs to be better understood. In this context, this study evaluated the role of cannabinoid receptor type 1 (CB1r) in brain redox state and aggressive-like behavior in Danio rerio (Zebrafish). For this, 64 animals were subdivided into groups: (a) Control (n=26), (b) ACEA (n=30) and (c) AM-251 (n=12), all treated with the drugs of interest: (a) Vehicle (NaCl 0.9%); (b) ACEA agonist 1 mg/kg; (c) 1 mg/kg AM-251 antagonist. The animals were isolated in pairs, without physical contact for 24 hours, followed by pre-treatment and after 30 minutes of pharmacokinetics, the fights were filmed for 30 minutes, the individuals were identified as Dominant or Subordinate and the brains were collected for evaluation of the state brain redox of these individuals. Our results demonstrate, for the first time, that the activation of CB1r by the ACEA agonist modulates aggressive-like behavior and, consequently, partially interferes with the establishment of social hierarchy in Zebrafish, through a redox-independent mechanism. We suggest, therefore, that acute treatment targeting CB1r is a useful neuropharmacological tool to elucidate the role of CES in social interaction and aggressive behavior, allowing a translation with numerous pathologies that have aggression as a behavioral disorder.