Departamento de Psicología Biológica y de la Salud, Facultad de Psicología, Universidad Autónoma de Madrid, Madrid, Spain.
Facultad de Educación y Psicología, Universidad Francisco de Vitoria, Madrid, Spain.
Addict Biol. 2022 Mar;27(2):e13158. doi: 10.1111/adb.13158.
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.
我们的目的是评估认知和情绪状态，以及青春期 C57BL/6J 雄性小鼠在 5 周双瓶选择方案（出生后第 21 天至第 52 天）后糖皮质激素受体 (GR)、促肾上腺皮质释放因子 (CRF) 和脑源性神经营养因子 (BDNF) 的表达变化。此外，我们还分析了在青春期晚期（第 62 天）观察到的行为和神经生物学效应是否持续到成年期（第 84 天）。行为测试表明，青春期早期的酒精摄入会增加焦虑样和强迫相关行为，这些行为在成年期仍持续存在。关于认知，工作记忆仅在青春期晚期的小鼠中发生改变，而在两个年龄段的小鼠中，物体位置测试的表现都受到损害。相比之下，新物体识别保持不变。免疫组织化学分析表明，青春期酒精摄入减少了扣带皮层、海马 CA1 层和中央杏仁核中的 BDNF+细胞。关于下丘脑-垂体-肾上腺轴（HPA）功能，酒精滥用增加了下丘脑室旁核和中央杏仁核中 GR 和 CRF 的表达。除此之外，GR 密度在额前皮质和基底外侧杏仁核中也更高，无论动物的年龄如何。我们的研究结果表明，青春期酒精暴露导致了长期的行为改变，以及与应激反应、情绪调节和认知相关的边缘脑区的 BDNF、GR 和 CRF 表达变化。
