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

摘要

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% v/v in water, i.g., 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, i.p., administered during scanning). Data were acquired on a Bruker 9.4T MR scanner with rats under dexmedetomidine sedation in combination with isoflurane. Frontolimbic network regions-of-interest (ROIs) 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 BOLD changes within all ROIs 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.