Heavy episodic drinking or
binge drinking during adolescence may elicit serious neurotoxic consequences in cerebral areas (e.g., the prefrontal cortex, i.e., PFC) and the hippocampus, delay the maturation of the brain and increase the probability of
drug abuse and dependence. The
endocannabinoid system plays an important role in neuroprotection by reducing oxidative stress and
neuroinflammation. In the present study, we aimed to investigate whether
URB597, an inhibitor of the metabolic
enzyme of the
endocannabinoid anandamide (AEA), altered the effects of acute and chronic alcohol administration beginning during rat adolescence on recognition memory,
neuroinflammation and
brain-derived neurotrophic factor (
BDNF) levels. The animals received
intraperitoneal injections of
URB597 (0.3 mg/Kg) or vehicle followed by the
oral administration of
ethanol (3 or 6 g/Kg) or distilled water for 3 consecutive days in one week (acute binging) or over 4 weeks (chronic binging). The groups were submitted to the novel object recognition task, and their PFCs and hippocampi were removed for analyses of the
cytokine and
BDNF levels.
URB597 potentiated long-term memory after the 3 mg/Kg acute alcohol administration. The chronic binge alcohol administration increased the
interferon (IFN)-γ and
tumor necrosis factor (TNF)-α levels in the PFC and hippocampus and the
interleukin (IL)-10 and
BDNF levels in the PFC, and these effects were prevented by
URB597. Our results indicate that the neuromodulation facilitated by AEA can reduce the neuroimmune response induced by the chronic administration of alcohol beginning in adolescence in rats.