Sex-dependent effects of short-term ethanol, energy drinks and acute noise exposure on hippocampal oxidative balance and glutamate transporter EAAT-1 during rat adolescence

It is known that human adolescents often consume ethanol (EtOH) alone or mixed with energy drinks (ED), especially in noisy environments. Although these agents impact the developing brain, their effects after brief exposure or when presented together remain unclear. Given that few animal studies in this subject are available, this research aimed to study the effects of a brief exposure to these stimuli on the oxidative state and EAAT-1 glutamate transporter levels in the developing rat hippocampus (HC). Adolescent Wistar rats were subjected to a two-bottle choice, limited access to drinking in the dark paradigm, for EtOH and EtOH+ED intake, for 4 days, and subsequent acute noise exposure. Next, hippocampal catalase activity, reactive oxygen species (ROS), glutaredoxin-1 (Grx-1) and glutamate transporter EAAT-1 levels were assessed. Results showed sex-dependent alterations after exposure to these stimuli: Females consuming EtOH had higher hippocampal ROS levels, which decreased when combined with noise; males showed reduced ROS levels only after noise exposure. No significant changes occurred in catalase activity, Grx-1, or EAAT-1 levels with EtOH and noise exposure in neither sex. Additionally, ED raised EtOH consumption in both sexes, normalizing ROS levels only in females when combined with EtOH. Finally, ED consumption altered Grx-1 and EAAT-1 levels in both sexes. In summary, brief exposure to these stimuli induced sex-dependent alterations, suggesting differentiated coping strategies between sexes. Whereas ED consumption may have antioxidant effects in some cases, it could also increase excitotoxicity risk. These novel findings raise questions for future research on the underlying corresponding mechanisms.