Introduction: Binge consumption of ethanol is an intermittent and episodic pattern of ingestion involved in several brain disorders that affect adolescents, considered more susceptible to damage that persists into adulthood. In the deleterious effects of ethanol, an important intoxication mechanism is the overproduction of adenosine, which causes hyperexcitability in its receptors, generating behavioral changes and oxidative stress. These receptors are antagonized by caffeine, a bioactive compound that can modulate the deleterious overactivation of ethanol. Objective: The aim of this study was to investigate the effects of caffeine administration on behavioral changes related to locomotion, anxiety, cognition and oxidative balance induced by ethanol in the binge drinking pattern during adolescence. In addition, it aims to assess the contribution of A2A receptors in the observed changes, including long-term potentiation (LTP). Material and Methods: Female Wistar rats (35 days old; n = 102) were allocated into six groups: control (distilled water, v.o), ethanol (3 g/kg/day; 3 days on-4 days off, v.o) , caffeine (10 mg/kg/day, v.o), caffeine + ethanol, A2A antagonist SCH58261 (0.1 mg/kg/day, intraperitoneal - i,p) and ethanol + SCH58261. The animals were submitted to open field behavioral tests, object recognition and elevated plus maze. The oxidative biochemistry parameters of trolox equivalent antioxidant capacity (TEAC), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) in the pre- frontal and hippocampus. LTP recordings in the medial prefrontal cortex (mPFC), ventral (vHip) and dorsal (dHIP) portions of the hippocampus of the control, ethanol, ethanol + SCH58261 and SCH58261 groups were evaluated through electrophysiology. Results: Caffeine prevented ethanol-induced behavioral impairments, including by blocking A2A receptors. In addition, it attenuated the oxidative stress induced by binge drinking by alternative A2A receptor pathways. Blockade of A2A receptors increased LTP levels in mPFC and vHIP, however decreased in dHIP. Conclusion: Caffeine showed neuroprotection in behavioral changes and oxidative stress induced by the binge drinking model in adolescent rats. In addition, blockade of A2A receptors mitigated the observed behavioral changes, with improvement of LTP levels in the prefrontal cortex and hippocampus, which suggests the contribution of this pathway to neuroprotection in deficits induced by ethanol exposure during adolescence.
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