Ana Contreras1, Lidia Morales1, Nuria Del Olmo2. 1. Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, Spain. 2. Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, Spain. Electronic address: nolmo@ceu.es.
Abstract
BACKGROUND: Binge drinking is a pattern of alcohol intake characterized by excessive and intermittent alcohol consumption over a very short period of time that is more used during adolescence. We aim to compare the lasting effects of a chronic-moderate vs. this intermittent-excessive way of alcohol intake during adolescence in spatial memory and in the expression of glutamatergic receptors and GSK3β activity. METHODS: Adolescent male Wistar rats were given ethanol/saline i.p. injections in four different groups: High-I (4 g/kg of a 25% (vol/vol) every 3 days), Low-I (1 g/kg of a 5% (vol/vol) every 3 days), M (0.3 g/kg of a 2.5% (vol/vol) daily) and Control (C, sterile isotonic saline daily). Rats received ethanol for up to five 3-day cycles. Spatial memory was measured by spontaneous alternation in the Y-Maze. Gene and protein expression of hippocampal proteins were also analysed. RESULTS: Both high- and low-intermittent ethanol administration produced spatial memory impairment and changes in glutamatergic receptors gene expression were observed regardless of the pattern of exposure. High doses of intermittent alcohol administration produced an increase of phosphorylation of GSK3β Ser9. Moreover, moderate alcohol administration produced a down-regulation of the AMPAR 2/3 ratio despite lack of spatial memory deficits. CONCLUSIONS: Excessive and intermittent ethanol exposure during adolescence impaired the spatial memory processes during adulthood regardless of the amount of alcohol administered. Moreover, chronic-moderate and intermittent pattern induced changes in the expression of glutamatergic receptors. In addition, high-intermittent ethanol exposure during adolescence inactivated GSK3β by increasing its phosphorylation in Ser9.
BACKGROUND: Binge drinking is a pattern of alcohol intake characterized by excessive and intermittent alcohol consumption over a very short period of time that is more used during adolescence. We aim to compare the lasting effects of a chronic-moderate vs. this intermittent-excessive way of alcohol intake during adolescence in spatial memory and in the expression of glutamatergic receptors and GSK3β activity. METHODS: Adolescent male Wistar rats were given ethanol/saline i.p. injections in four different groups: High-I (4 g/kg of a 25% (vol/vol) every 3 days), Low-I (1 g/kg of a 5% (vol/vol) every 3 days), M (0.3 g/kg of a 2.5% (vol/vol) daily) and Control (C, sterile isotonic saline daily). Rats received ethanol for up to five 3-day cycles. Spatial memory was measured by spontaneous alternation in the Y-Maze. Gene and protein expression of hippocampal proteins were also analysed. RESULTS: Both high- and low-intermittent ethanol administration produced spatial memory impairment and changes in glutamatergic receptors gene expression were observed regardless of the pattern of exposure. High doses of intermittent alcohol administration produced an increase of phosphorylation of GSK3β Ser9. Moreover, moderate alcohol administration produced a down-regulation of the AMPAR 2/3 ratio despite lack of spatial memory deficits. CONCLUSIONS: Excessive and intermittent ethanol exposure during adolescence impaired the spatial memory processes during adulthood regardless of the amount of alcohol administered. Moreover, chronic-moderate and intermittent pattern induced changes in the expression of glutamatergic receptors. In addition, high-intermittent ethanol exposure during adolescence inactivated GSK3β by increasing its phosphorylation in Ser9.