Neonatal alcohol exposure reduces number of parvalbumin-positive interneurons in the medial prefrontal cortex and impairs passive avoidance acquisition in mice deficits not rescued from exercise.

Developmental alcohol exposure causes a host of cognitive and neuroanatomical abnormalities, one of which is impaired executive functioning resulting from medial prefrontal cortex (mPFC) damage. This study determined whether third-trimester equivalent alcohol exposure reduced the number of mPFC GABAergic parvalbumin-positive (PV+) interneurons, hypothesized to play an important role in local inhibition of the mPFC. The impact on passive avoidance learning and the therapeutic role of aerobic exercise in adulthood was also explored. Male C57BL/6J mice received either saline or 5g/kg ethanol (two doses, two hours apart) on PD 5, 7, and 9. On PD 35, animals received a running wheel or remained sedentary for 48days before behavioral testing and perfusion on PD 83. The number of PV+ interneurons was stereologically measured in three separate mPFC subregions: infralimbic, prelimbic and anterior cingulate cortices (ACC). Neonatal alcohol exposure decreased number of PV+ interneurons and volume of the ACC, but the other regions of the mPFC were spared. Alcohol impaired acquisition, but not retrieval of passive avoidance, and had no effect on motor performance on the rotarod. Exercise had no impact on PV+ cell number, mPFC volume, or acquisition of passive avoidance, but enhanced retrieval in both control and alcohol-exposed groups, and enhanced rotarod performance in the control mice. Results support the hypothesis that part of the behavioral deficits associated with developmental alcohol exposure are due to reduced PV+ interneurons in the ACC, but unfortunately exercise does not appear to be able to reverse any of these deficits.