Estudo do efeito neuroprotetor do inibidor da faah urb597 na neurotoxicidade causada pelo consumo de álcool em binge por ratos adolescentes

Abstract

The heavy episodic drinking or binge drinking of alcohol during adolescence may bring serious neurotoxic consequences, especially to cerebral areas such as the prefrontal cortex (PFC), late maturing and involvement in the abuse and drug dependence in cognitive processes, and the hippocampus, related to declarative memory. The endocannabinoid system seems to be related to neuroprotection, since many studies demonstrate that the activation of its receptors reduces the oxidative stress and the inflammatory response in central nervous system diseases. Considering the hypotheses that the endocannabinoids may protect the brain from damage caused by the consumption of ethanol in binge drinking, this study investigated the effect of the metabolic enzyme of the anandamida endocannabinoid (fatty acid amide hydrolase – FAAH) inhibitor, the URB597, in the oxidative stress and neuroinflammation induced by the consumption of alcohol in acute or chronic binge drinking in adolescent rats. Each of the animals were submitted to the Intraperitoneal injection (IP) of URB597 (0.3 mg/kg) or also followed by, after 40 minutes, the Intragastric injection (IG) of ethanol (3 and 6 g/kg) or distilled water in 3 consecutive sessions (acute binging), or 3 consecutive sessions during a 4 week period (chronic binging). The animals of the acute and chronic binging groups were also submitted to object recognition tests. The results demonstrated that the alcohol in acute binge drinking in 3 and 6 g/kg doses and chronic binge drinking in 6 g/kg doses induced oxidative stress in the PFC, and the pretreatment with URB597 reduced this effect. The consumption of alcohol in chronic binge drinking in 3 and 6 g/kg doses raised the levels of neurotrophin BDNF and the proinflammatory cytokines TNF-α in the PFC and hippocampus of the adolescent rats. The pretreatment with URB597 was able to decrease the levels of BDNF and TNF-α. The consumption of alcohol in binge drinking in 3 g/hg doses impaired the long-term memory (24 h) of adolescent rats in relation to recognizing objects, and the pretreatment with URB597 reduced this loss. The chronic binge drinking of alcohol in 6 g/kg doses impaired the long-term memory in relation to object recognition testing, but the pretreatment with URB597 was unable to decrease the effect of the impairment. In summary, the results of this study indicate the involvement of the endocannabinoid system in the neuroprotection against neurotoxicity caused by the consumption of binge drinking alcohol in adolescent rats.