Intermittent-Excessive and Chronic-Moderate Ethanol Intake during Adolescence Impair Spatial Learning, Memory and Cognitive Flexibility in the Adulthood

• Published in: Neuroscience Vol. 418; pp. 205 - 217
• Main Authors: Contreras, Ana, Polín, Eduardo, Miguéns, Miguel, Pérez-García, Carmen, Pérez, Vicente, Ruiz-Gayo, Mariano, Morales, Lidia, Del Olmo, Nuria
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 15.10.2019
• Subjects: adolescence; binge drinking; GSK3β; hippocampus; long-term depression; memory; C; memory; hippocampus; fEPSPs; long-term depression; PND; EtOH; LTP; CM; i.p; binge drinking; AMPAR; GSK3β; ANOVA; BW; adolescence; NMDAR; KRB; IE; LTD; RAM
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2019.08.051

Intermittent and excessive ethanol consumption over very short periods of time, known as binge drinking, is common in the adolescence, considered a vulnerable period to the effects of alcohol in terms of cognitive performance. One of the brain functions most drastically affected by ethanol in adolescent individuals seems to be spatial learning and memory dependent on the hippocampus. In the current study we have focused on the long-lasting effects on spatial learning and memory of intermittent and excessive alcohol consumption compared to chronic and moderate alcohol exposure during adolescence. Five-week old male Wistar rats consumed ethanol for 24 days following two different self-administration protocols that differed in the intake pattern. Spatial learning and memory were evaluated in the radial arm maze. Hippocampal synaptic plasticity was assessed by measuring field excitatory postsynaptic potentials. Hippocampal expression of AMPA and NMDA receptor subunits as well as levels of phosphorylated Ser9-GSK3β (the inactive form of GSK3β) were also quantified. Our results show that both patterns of ethanol intake during adolescence impair spatial learning, memory and cognitive flexibility in the adulthood in a dose-dependent way. Nevertheless, changes in synaptic plasticity, gene expression and levels of inactive GSK3β depended on the pattern of ethanol intake. •High doses of intermittent and excessive ethanol intake during adolescence impair spatial memory.•Cognitive flexibility is impaired after all the patterns and doses of ethanol used.•Intermittent and excessive ethanol administration inhibits hippocampal LTD.•Chronic-moderate ethanol intake regulates gene and protein glutamatergic expression.•Alcohol intake inactivates GSK3β, which correlated with memory impairment and may explain LTD deficits.