Long-term consequences of alcohol use in early adolescent mice: Focus on neuroadaptations in GR, CRF and BDNF.
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2022
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Addiction Biology
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Abstract
Our aim was to assess the cognitive and emotional state, as well as related-changes
in the glucocorticoid receptor (GR), the corticotropin-releasing factor (CRF) and the
brain-derived neurotrophic factor (BDNF) expression of adolescent C57BL/6J male
mice after a 5-week two-bottle choice protocol (postnatal day [pd]21 to pd52). Additionally,
we wanted to analyse whether the behavioural and neurobiological effects
observed in late adolescence (pd62) lasted until adulthood (pd84). Behavioural testing
revealed that alcohol during early adolescence increased anxiety-like and
compulsive-related behaviours, which was maintained in adulthood. Concerning cognition,
working memory was only altered in late adolescent mice, whereas object
location test performance was impaired in both ages. In contrast, novel object recognition
remained unaltered. Immunohistochemical analysis showed that alcohol during
adolescence diminished BDNF+ cells in the cingulate cortex, the hippocampal CA1
layer and the central amygdala. Regarding hypothalamic-pituitary-adrenal axis (HPA)
functioning, alcohol abuse increased the GR and CRF expression in the hypothalamic
paraventricular nucleus and the central amygdala. Besides this, GR density was also
higher in the prelimbic cortex and the basolateral amygdala, regardless of the animals'
age. Our findings suggest that adolescent alcohol exposure led to long-term behavioural
alterations, along with changes in BDNF, GR and CRF expression in limbic brain
areas involved in stress response, emotional regulation and cognition.
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Adolescence, Ethanol, Two-bottle choice