Prenatal methotrexate exposure delays onset of low Mg(2+)-induced epileptiform discharges in the entorhinal cortex

We determined the effects of prenatal exposure to DNA synthesis inhibitor methotrexate (MTX) on: (a) the susceptibility to low Mg(2+)-induced epileptiform activity in deep layers (IV-V) of medial entorhinal cortex in vitro; and (b) neuronal counts in this area. Low Mg(2+)-induced discharges developed significantly later in slices from prenatally MTX-exposed rats than in control slices. Neuronal counts were increased in the layer V of medial entorhinal cortex of prenatally MTX-exposed rats. Results indicate that: (a) MTX-induced prenatal brain DNA impairment is antiepileptogenic; and (b) simple increases in neuronal numbers may not be associated with epileptogenic effects.