Adolescent alcohol exposure decreases frontostriatal resting‐state functional connectivity in adulthood

摘要

Abstract 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.