Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, USA.
Department of Neurology, University of North Carolina, Chapel Hill, NC, USA.
Addict Biol. 2018 Mar;23(2):810-823. doi: 10.1111/adb.12530. Epub 2017 Jul 9.
Connectivity of the prefrontal cortex (PFC) matures through adolescence, coinciding with emergence of adult executive function and top-down inhibitory control over behavior. Alcohol exposure during this critical period of brain maturation may affect development of PFC and frontolimbic connectivity. Adult rats exposed to adolescent intermittent ethanol (AIE; 5 g/kg ethanol, 25 percent v/v in water, intragastrically, 2-day-on, 2-day-off, postnatal day 25-54) or water control underwent resting-state functional MRI to test the hypothesis that AIE induces persistent changes in frontolimbic functional connectivity under baseline and acute alcohol conditions (2 g/kg ethanol or saline, intraperitoneally administered during scanning). Data were acquired on a Bruker 9.4-T MR scanner with rats under dexmedetomidine sedation in combination with isoflurane. Frontolimbic network regions-of-interest for data analysis included PFC [prelimbic (PrL), infralimbic (IL), and orbitofrontal cortex (OFC) portions], nucleus accumbens (NAc), caudate putamen (CPu), dorsal hippocampus, ventral tegmental area, amygdala, and somatosensory forelimb used as a control region. AIE decreased baseline resting-state connectivity between PFC subregions (PrL-IL and IL-OFC) and between PFC-striatal regions (PrL-NAc, IL-CPu, IL-NAc, OFC-CPu, and OFC-NAc). Acute ethanol induced negative blood-oxygen-level-dependent changes within all regions of interest examined, along with significant increases in functional connectivity in control, but not AIE animals. Together, these data support the hypothesis that binge-like adolescent alcohol exposure causes persistent decreases in baseline frontolimbic (particularly frontostriatal) connectivity and alters sensitivity to acute ethanol-induced increases in functional connectivity in adulthood.
前额叶皮层（PFC）的连接性在青春期成熟，与成年执行功能和自上而下的行为抑制控制的出现相吻合。在大脑成熟的这个关键时期暴露于酒精可能会影响 PFC 和额眶皮质连接的发育。在青春期间歇性乙醇（AIE；5 g/kg 乙醇，25%v/v 在水中，胃内，2 天 ON，2 天 OFF，出生后第 25-54 天）或水对照下接受过休息状态功能磁共振成像（MRI）检查的成年大鼠，以测试 AIE 是否在基线和急性酒精条件下（2 g/kg 乙醇或生理盐水，腹腔内给药，扫描期间）诱导额眶皮质功能连接的持续变化。数据是在 Bruker 9.4-T MR 扫描仪上采集的，大鼠在右美托咪定镇静下，同时使用异氟烷。用于数据分析的额眶皮质网络感兴趣区包括前额叶皮层（PrL、IL 和眶额皮层（OFC）部分）、伏隔核（NAc）、尾状核壳（CPu）、背侧海马、腹侧被盖区、杏仁核和体感前肢作为对照区。AIE 降低了 PFC 亚区（PrL-IL 和 IL-OFC）之间以及 PFC-纹状体区域（PrL-NAc、IL-CPu、IL-NAc、OFC-CPu 和 OFC-NAc）之间的基线静息状态连接性。急性乙醇诱导所有感兴趣区域内的负血氧水平依赖变化，同时在对照动物中而非 AIE 动物中，功能连接性显著增加。这些数据共同支持这样的假设，即 binge-like 青少年酒精暴露导致基线额眶皮质（特别是额纹状体）连接性持续下降，并改变了对成年期急性乙醇诱导的功能连接性增加的敏感性。
