Long‐term consequences of alcohol use in early adolescent mice: Focus on neuroadaptations in GR, CRF and BDNF

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.

Immersive virtual plus-maze to examine behavior and psychophysiological-related variables in young people with problematic alcohol and cannabis consumption

“…Considering these aspects, our AU group made fewer entries into the open arms compared to the CO group and both experimental groups (AU and AU + C) spent fewer time at the end of the open arms and displayed a lower time by look index suggesting a more anxious profile of exploration. These results suggest a cross-species similarity between animal models and humans because rodents with ethanol consumption during their young adulthood usually also show anxiety-like behaviors in the EPM ( Hefner and Holmes, 2007 ; Sampedro-Piquero et al, 2022 ). Besides, and according to the study of Madeira et al (2021) , the open arm avoidance observed in our experimental groups could be related to acrophobia, as these authors proposed, or trait anxiety owing to the negative correlation observed between the behavioral variables and the score in this questionnaire (STAI-t) in the AU group.…”

“…In this regard, both clinical and preclinical studies have reported that an increase in alcohol consumption is associated with stress ( Kirsch and Lippard, 2022 ). Other studies in rodent models have also shown that early alcohol consumption induces a long-term enhancement of anxiety-like behaviors ( Sampedro-Piquero et al, 2022 ; Sánchez-Marín et al, 2022 ). Considering these findings, early life stress is a recognized risk factor for developing common psychiatric disorders, such as depression and anxiety, as well as a higher vulnerability to suffer substance use disorders ( Cabanis et al, 2021 ).…”

Consequences of adolescent drug use

“…In addition, AAE is known to trigger a series of behavioral effects than can often persist into adulthood, many of which are related to anxiety-and depression-like behavior [40][41][42][43][44]. For example, AAE is associated with increased rates of major depressive disorder [45,46], particularly in females [47].…”

BDNF and its Role in the Alcohol Abuse Initiated During Early Adolescence: Evidence from Preclinical and Clinical Studies

“…Most of these programs were initially developed for adults and have been modified for adolescents, so they do not consider the particularities of this age group. Consequently, there is a need to explore other alternatives to treatment that, alone or in combination with existing ones, represent an improvement in treatment, because cognitive-behavioral alterations after adolescent binge drinking seem to persist into middle age, despite abstinence [ 220 , 221 ].…”