Morphine exposure alters Fos expression in a sex-, age-, and brain region-specific manner during adolescence.
Morphine exposure alters Fos expression in a sex-, age-, and brain region-specific manner during adolescence.
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青春期期间，吗啡暴露会以性别、年龄和大脑区域特异性的方式改变 Fos 的表达。
DOI：
10.1002/dev.22186
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发表时间：
2021
影响因子：
2.2
通讯作者：
Kopec,AM
中科院分区：
文献类型：
--
作者：
Figueroa,C;Yang,H;DiSpirito,J;Bourgeois,JR;Kalyanasundaram,G;Doshi,I;Bilbo,SD;Kopec,AM
人类和临床前动物模型的数据清楚地表明青春期期间的药物暴露，当大脑的“奖励”回路发育时，会增加晚年物质使用和其他精神健康障碍的风险。人类数据表明，在青春期早期和晚期可以观察到不同的神经和行为后遗症。然而，大多数啮齿动物模型的研究都比较了单个青少年年龄与成熟成年年龄的比较，而且通常只针对雄性。在此，我们试图确定对阿片类吗啡的急性反应是否也会因青春期和性别而异。通过量化青春期不同阶段（青春期前、青春期早期、中期和晚期）和多个奖赏区域（前额皮质、伏核、尾状核/壳核）的 Fos 阳性细胞（神经活动的代表），我们确定对急性吗啡的神经反应高度依赖于青少年的年龄、性别和大脑区域。这些数据表明，青少年阿片类药物暴露后果的异质性可能是由于个体奖励处理区域的年龄和性别特异性发育状况所致。在未来的研究中，将青春期内的年龄作为自变量来全面了解健康或异常的奖励相关神经发育非常重要。
Data in both humans and preclinical animal models clearly indicate drug exposure during adolescence, when the “reward” circuitry of the brain develops, increases the risk of substance use and other mental health disorders later in life. Human data indicate that different neural and behavioral sequelae can be observed in early versus late adolescence. However, most studies with rodent models examine a single adolescent age compared to a mature adult age, and often only in males. Herein, we sought to determine whether the acute response to the opioid morphine would also differ across adolescence, and by sex. By quantifying Fos positive cells, a proxy for neural activity, at different stages during adolescence (pre‐, early, mid‐, and late adolescence) and in multiple reward regions (prefrontal cortex, nucleus accumbens, caudate/putamen), we determined that the neural response to acute morphine is highly dependent on adolescent age, sex, and brain region. These data suggest that heterogeneity in the consequences of adolescent opioid exposure may be due to age‐ and sex‐specific developmental profiles in individual reward processing regions. In future studies, it will be important to add age within adolescence as an independent variable for a holistic view of healthy or abnormal reward‐related neural development.