Repeated cycles of binge-like ethanol exposure induce immediate and delayed neurobehavioral changes and hippocampal dysfunction in adolescent female rats

•Single cycle of ethanol treatment in mid-adolescence elicits anxiety-like profile.•Adolescent binge multiple cycles impair memory related to GFAP and BDNF alterations.•Adolescent repeated binge-like anxiety persists even in the long-lasting withdrawal.•Memory damage after adolescent binge cycles re...

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Published in:Behavioural brain research 2018-09, Vol.350, p.99-108
Main Authors: Fernandes, Luanna M.P., Cartágenes, Sabrina C., Barros, Mayara A., Carvalheiro, Taiana C.V.S., Castro, Nair C.F., Schamne, Marissa G., Lima, Rafael R., Prediger, Rui D., Monteiro, Marta C., Fontes-Júnior, Enéas A., Cunha, Rodrigo A., Maia, Cristiane S.F.
Format: Article
Language:English
Subjects:
Adolescence
Animals
Anxiety
Anxiety - etiology
Anxiety - physiopathology
Astrogliosis
BDNF
Binge drinking
Binge Drinking - physiopathology
Binge Drinking - psychology
Cognition
Female
Glial Fibrillary Acidic Protein - metabolism
Hippocampus - drug effects
Hippocampus - growth & development
Hippocampus - physiopathology
Memory Disorders - etiology
Memory Disorders - physiopathology
Rats, Wistar
Sexual Maturation
Time Factors
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Summary:•Single cycle of ethanol treatment in mid-adolescence elicits anxiety-like profile.•Adolescent binge multiple cycles impair memory related to GFAP and BDNF alterations.•Adolescent repeated binge-like anxiety persists even in the long-lasting withdrawal.•Memory damage after adolescent binge cycles recovers in the long-term withdrawal. Binge-like ethanol intake (BEI) is a socioeconomical problem among adolescents and increasingly affects women. BEI can leave a long-term imprint in the brain, but it is unknown if its effect on cognition and anxiety is cumulative on repeated binge-ethanol episodes. We now submitted female Wistar rats to repeated cycles of binge-like ethanol treatment by intragastrically administering ethanol (3.0 g/kg/day, 20% w/v ethanol; 3 days on/4 days off) starting at postnatal day 35 (PND35). To investigate the short-term effects of BEI during adolescence, rats underwent 1 or 4 cycles of BEI, being evaluated at PND37 and PND58, respectively: both groups displayed anxiety-like behavior in the open field and elevated plus-maze tests, as well as short-term memory deficits in the object recognition task; this was associated with transient decreases of BDNF levels and increases of GFAP levels in the hippocampus. To evaluate the short- and long-lasting effects of BEI in adulthood, rats were subjected to 8 cycles of BEI and evaluated after 7.5 h (PND86) or after 14 days of ethanol withdrawal (PND100). This caused a persistent anxiogenic profile whereas recognition memory was impaired on the short-term, but not 14 days post-administration. The reduced BDNF level observed shortly after BEI recovered upon withdrawal, whereas increased GFAP immunoreactivity was persistent up to 14 days post-administration in adulthood. These findings show that repeated binge-like ethanol episodes from adolescence to adulthood in female rats cause consistent and long-term alterations of anxiety and hippocampal astrogliosis, whereas they trigger a recognition memory deficit paralleled by lower hippocampal BDNF levels, both recovering upon ethanol withdrawal.
ISSN:0166-4328
1872-7549
DOI:10.1016/j.bbr.2018.05.007