Binge-like Alcohol Exposure in Adolescence: Behavioural, Neuroendocrine and Molecular Evidence of Abnormal Neuroplasticity… and Return

Brancato, Anna; Castelli, Vincenzo Parenti; Lavanco, Gianluca; Tringali, Giuseppe; Micale, Vincenzo; Kuchař, Martin; D’Amico, Cesare; Pizzolanti, Giuseppe; Feo, Salvatore; Cannizzaro, Carla

doi:10.3390/biomedicines9091161

Cited by 25 publications

(46 citation statements)

References 124 publications

(158 reference statements)

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“…BAW rats were exposed to alcohol in an intermittent binge-like alcohol paradigm during adolescence (PND [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54]. The 25% alcohol solution was daily prepared and administered per os (38), at the dosage of 3.5 g/kg (39), 3 days a week, every other day, for a total of 9 exposure, as previously described (30). CTRL rats were given an isovolumetric amount of tap water on the same exposure days.…”

Section: Anxiety-like Phenotype and Stress Reactivity Evaluation In A...mentioning

confidence: 99%

“…Therefore, in an attempt to crack the chicken-or-egg question, we exploited the animal model, which allows analyzing complex pathological constructs by isolating their single behavioral features and studying their determinants. We explored the relationship between the exposure to a binge-like alcohol paradigm in adolescence, known to induce multilevel maladaptive plasticity (30) and the development of a vulnerable endophenotype for emotional dysregulation and negative affective state in the rat. In detail, we investigated ethologically-relevant behavioral and endocrine responses to emotionally-salient environmental stimuli, such as novelty and social stress as they represent common challenges adolescents face.…”

Section: Introductionmentioning

confidence: 99%

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Alcohol binge drinking in adolescence and psychological profile: Can the preclinical model crack the chicken-or-egg question?

et al. 2022

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During adolescence, internal and external factors contribute to engaging with alcohol binge drinking (ABD), putting at risk the neurodevelopment of brain regions crucial for emotional control and stress coping. This research assessed the prevalence of ABD in late adolescent students of Southern Italy and characterized their psychological profile and drinking motives. Translational effects of alcohol binge drinking in the animal model were also studied. Seven hundred and fifty-nine high school students of both sexes (aged 18–20) were recruited. Alcohol Use Disorder Identification Test-Consumption (AUDIT-C), Drinking Motives Questionnaire-Revised Short Form, Millon Clinical Multiaxial Inventory-Third Ed., State-Trait Anxiety Inventory, Connor-Davidson Resilience Scale, and Basic Self-Esteem Scale identified alcohol habits, drinking motives, and psychopathological profile. Eighty-five percentage of the students drank alcohol and 28% of them engaged in ABD; AUDIT-C correlated with enhancement, coping, and conformity motives. ABD was related to a greater likelihood of presenting clinical syndromes and personality disorders, as well as low resilience and self-esteem. Thereafter, in the pre-clinical model, adolescent male rats were exposed to alcohol (3.5 g/kg) in an intermittent binge-like paradigm and tested during prolonged abstinence. Rats were evaluated for anxiety-like behavior, motivated behaviors, resilience, and stress response following a psychosocial challenge. Binge-like alcohol-exposed adolescent rats displayed high integrated z-score for social- and novelty-induced anxiety, altered motivation-driven output, decreased resilience, and a blunted HPA axis response to psychosocial stress, with respect to respective controls. Our data confirm that ABD is the chosen pattern of drinking in a significant percentage of high school students in Southern Italy, and highlights AUDIT-C score as a relevant parameter able to predict the occurrence of affective disturbances. The evidence from the preclinical model shows that ABD produces detrimental consequences in the adolescent rat brain, resulting in negative affect, emotional dysregulation, and aberrant stress response, pointing to decreasing excessive alcohol drinking as a primary goal for the global act for brain health.

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Section: Anxiety-like Phenotype and Stress Reactivity Evaluation In A...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alcohol binge drinking in adolescence and psychological profile: Can the preclinical model crack the chicken-or-egg question?

et al. 2022

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“…Our study analyzed levels of proteins involved in regulation of stress responses at 24 h of abstinence following continuous ethanol drinking. We acknowledge that distinct changes in these protein levels could occur at different time points of the procedure due to plasticity associated with the effects of ethanol and PS (e.g., Brancato et al, 2021 ). Our prior work observed significant alterations in hippocampal protein levels of two proteins involved in synaptic plasticity (ARC or activity-regulated cytoskeletal protein and synaptophysin; Devaud et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Sensitivity and Resilience to Predator Stress-Enhanced Ethanol Drinking Is Associated With Sex-Dependent Differences in Stress-Regulating Systems

Alavi

Ryabinin

Helms

et al. 2022

Front. Behav. Neurosci.

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Stress can increase ethanol drinking, and evidence confirms an association between post-traumatic stress disorder (PTSD) and the development of alcohol use disorder (AUD). Exposure to predator odor is considered a traumatic stressor, and predator stress (PS) has been used extensively as an animal model of PTSD. Our prior work determined that repeated exposure to intermittent PS significantly increased anxiety-related behavior, corticosterone levels, and neuronal activation in the hippocampus and prefrontal cortex in naïve male and female C57BL/6J mice. Intermittent PS exposure also increased subsequent ethanol drinking in a subgroup of animals, with heterogeneity of responses as seen with comorbid PTSD and AUD. The present studies built upon this prior work and began to characterize “sensitivity” and “resilience” to PS-enhanced drinking. Ethanol drinking was measured during baseline, intermittent PS exposure, and post-stress; mice were euthanized after 24-h abstinence. Calculation of median and interquartile ranges identified “sensitive” (>20% increase in drinking over baseline) and “resilient” (no change or decrease in drinking from baseline) subgroups. Intermittent PS significantly increased subsequent ethanol intake in 24% of male (↑60%) and in 20% of female (↑71%) C57BL/6J mice in the “sensitive” subgroup. Plasma corticosterone levels were increased significantly after PS in both sexes, but levels were lower in the “sensitive” vs. “resilient” subgroups. In representative mice from “sensitive” and “resilient” subgroups, prefrontal cortex and hippocampus were analyzed by Western Blotting for levels of corticotropin releasing factor (CRF) receptor 1, CRF receptor 2, CRF binding protein, and glucocorticoid receptor, vs. separate naïve age-matched mice. In prefrontal cortex, CRF receptor 1, CRF receptor 2, CRF binding protein, and glucocorticoid receptor levels were significantly higher in “sensitive” vs. naïve and “resilient” mice only in females. In hippocampus, CRF receptor 1, CRF receptor 2 and glucocorticoid receptor levels were significantly lower in “resilient” vs. naïve and “sensitive” mice across both sexes. These results indicate that sex strongly influences the effects of ethanol drinking and stress on proteins regulating stress and anxiety responses. They further suggest that targeting the CRF system and glucocorticoid receptors in AUD needs to consider the comorbidity of PTSD with AUD and sex of treated individuals.

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“…The test was carried out in a moderately illuminated room, as previously described [ 45 , 46 , 47 ]. A total of two unfamiliar rats, which had approximately the same weight and had received identical prenatal (MAM or saline) and postnatal (AM251 or VHC) treatment, were placed in opposite corners of a metal arena (120 lux, 60 × 60 × 60 cm) for 10 min.…”

Section: Methodsmentioning

confidence: 99%

Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like Alterations in the Neurodevelopmental MAM Model of Schizophrenia

et al. 2022

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In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of Sprague-Dawley rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produces long-lasting behavioral alterations such as social withdrawal and cognitive impairment in adulthood, mimicking a schizophrenia-like phenotype. These abnormalities were preceded at neonatal age both by the delayed appearance of neonatal reflexes, an index of impaired brain maturation, and by higher 2-arachidonoylglycerol (2-AG) brain levels. Schizophrenia-like deficits were reversed by early treatment [from postnatal day (PND) 2 to PND 8] with the CB1 antagonist/inverse agonist AM251 (0.5 mg/kg/day). By contrast, early CB1 blockade affected the behavioral performance of control rats which was paralleled by enhanced 2-AG content in the prefrontal cortex (PFC). These results suggest that prenatal MAM insult leads to premorbid anomalies at neonatal age via altered tone of the endocannabinoid system, which may be considered as an early marker preceding the development of schizophrenia-like alterations in adulthood.

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Binge-like Alcohol Exposure in Adolescence: Behavioural, Neuroendocrine and Molecular Evidence of Abnormal Neuroplasticity… and Return

Cited by 25 publications

References 124 publications

Alcohol binge drinking in adolescence and psychological profile: Can the preclinical model crack the chicken-or-egg question?

Alcohol binge drinking in adolescence and psychological profile: Can the preclinical model crack the chicken-or-egg question?

Sensitivity and Resilience to Predator Stress-Enhanced Ethanol Drinking Is Associated With Sex-Dependent Differences in Stress-Regulating Systems

Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like Alterations in the Neurodevelopmental MAM Model of Schizophrenia

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