Effects of fetal treatment with methylazoxymethanol acetate at various gestational dates on the neurochemistry of the adult neocortex of the rat.

The effects of gestational date (13, 14, 15, and 17 days) or administration of methylazoxymethanol acetate (20 mg/kg) on the cortical synaptic chemistry and morphology of the rat has been examined in adult offspring. Treatment at 13 days of gestation (DG) resulted in cortical hypoplasia that affected primarily the deep layers whereas treatment at 14 and 15 days gestation caused a severe hypoplasia of cortical neurons above layer V and a 66 to 77% reduction in cortical mass. The 17-DG treatment caused only a 20% reduction in cortical weight with effects apparent only in the superficial layers. At no treatment date did the specific activity of glutamate decarboxylase differ significantly from control. In contrast, presynaptic markers for noradrenergic (tyrosine hydroxylase and norepinephrine) and for serotonergic (serotonin) terminals were increased in concentration in direct proportion to the degree of cortical hypoplasia. The specific activity of choline acetyltransferase was significantly increased at all treatment dates but total activity per cortical slab was significantly reduced on treatment days 13-15.