Pervasive hyperactivity and long-term learning impairments in rats with induced micrencephaly from prenatal exposure to methylazoxymethanol.

Pregnant Long-Evans rats were given a single i.p. injection of 30 mg/kg of methylazoxymethanol (MAM) acetate or saline on day 14 of gestation (vaginal plug = day 0). All litters were reduced to 8 at birth and were reared by their biological dams. Between 49-192 days of age all offspring were examined on open-field, figure-8 (at two different ages), and hole-board tests of activity, as well as passive avoidance and Biel water maze tests of learning (also at two different ages). The MAM offspring showed no increase in mortality, but weighed less than controls, a difference that remained relatively constant throughout the experiment. At 204-215 days of age the MAM offspring were confirmed to be micrencephalic, a known effect of this drug at this dose and exposure period. On all tests of activity the MAM offspring were markedly hyperactive. The female progeny also exhibited a pronounced impairment of normal activity habituation patterns. The MAM males, however, showed a marked impairment of passive avoidance performance, while the females did not. At 2 months of age the MAM offspring also showed a pronounced deficit in learning a water maze. This maze deficit had not abated when tested again at 6 months of age. The MAM induced brain and behavioral abnormalities provide a potentially useful animal model of congenital micrencephaly and associated mental retardation.

Augmented memory loss in aging mice after one embryonic exposure to alcohol.

Prenatal exposure to alcohol can produce behavioral and cognitive deficits even in the absence of dysmorphic facial features. In a mouse model, we tested whether embryonic exposure to alcohol could exacerbate functional loss as animals age. Normal-appearing offspring were selected from litters produced by C57Bl/6J mice that had been gavaged with one teratogenic dose (5.8 g/kg) of ethyl alcohol during organogenesis on the 9th day of gestation. In adulthood, the offspring suffered a deficit in long-term retention, but not acquisition, of a place learning task. Although barely detectable in young adults, the retention deficit was severe in aging mice. These findings demonstrate that the functional deficits resulting from embryonic exposure to alcohol can interact with those of aging.