Laboratorio de Fisiologia e Farmacologia do Sistema Nervoso Central, Department of Pharmacology, Universidade Federal do Parana, Curitiba, PR, Brazil.
Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Sci Rep. 2024 Jun 14;14(1):13775. doi: 10.1038/s41598-024-64036-1.
Exposure to alcohol during adolescence impacts cortical and limbic brain regions undergoing maturation. In rodent models, long-term effects on behavior and neurophysiology have been described after adolescent intermittent ethanol (AIE), especially in males. We hypothesized that AIE in female rats increases conditional approach to a reward-predictive cue and corresponding neuronal activity in the orbitofrontal cortex (OFC) and nucleus accumbens (NAc). We evaluated behavior and neuronal firing after AIE (5 g/kg intragastric) or water (CON) in adult female rats. Both AIE and CON groups expressed a ST phenotype, and AIE marginally increased sign-tracking (ST) and decreased goal-tracking (GT) metrics. NAc neurons exhibited phasic firing patterns to the conditional stimulus (CS), with no differences between groups. In contrast, neuronal firing in the OFC of AIE animals was greater at CS onset and offset than in CON animals. During reward omission, OFC responses to CS offset normalized to CON levels, but enhanced OFC firing to CS onset persisted in AIE. We suggest that the enhanced OFC neural activity observed in AIE rats to the CS could contribute to behavioral inflexibility. Ultimately, AIE persistently impacts the neurocircuitry of reward-motivated behavior in female rats.
青春期接触酒精会影响正在成熟的大脑皮质和边缘区域。在啮齿动物模型中，青春期间断性乙醇暴露（AIE）后，尤其是在雄性中，其对行为和神经生理学的长期影响已被描述。我们假设，AIE 会增加雌性大鼠对奖励预测线索的条件趋近反应以及眶额皮质（OFC）和伏隔核（NAc）的相应神经元活动。我们评估了 AIE（5g/kg 灌胃）或水（CON）处理后的成年雌性大鼠的行为和神经元放电。AIE 和 CON 组均表现出 ST 表型，AIE 组轻度增加了标志跟踪（ST），降低了目标跟踪（GT）指标。NAc 神经元对条件刺激（CS）表现出相位性放电模式，两组之间没有差异。相比之下，AIE 动物的 OFC 神经元在 CS 起始和结束时的放电比 CON 动物更强。在奖励缺失期间，OFC 对 CS 结束的反应与 CON 水平正常化，但 AIE 组对 CS 起始的 OFC 放电增强持续存在。我们认为，AIE 大鼠对 CS 的增强的 OFC 神经活动可能有助于行为的不灵活性。最终，AIE 持续影响雌性大鼠奖赏动机行为的神经回路。
