Increased seizure susceptibility induced by prenatal methamphetamine exposure in adult female rats is not affected by early postnatal cross-fostering.

Our previous studies repeatedly demonstrated that prenatal methamphetamine (MA) exposure alters seizure susceptibility in adult rats. Both the inhibitory GABA system and the excitatory NMDA system play a role in the effect of MA on epileptic seizures. On the basis of our previous behavioral results, the effect of cross-fostering on seizure susceptibility in adult female rats was examined in the present study. Bicuculline (GABA(A) receptor antagonist) and NMDA (NMDA receptor agonist) were used to induce seizures in adult female offspring exposed to MA in the prenatal and/or preweaning periods. Female dams were injected with MA (5mg/kg daily) or physiological saline (S) for approximately 9 weeks [about 3 weeks prior to impregnation, for the entire gestation period (22 days), and in the preweaning period (21 days)]. Absolute controls (C) did not receive any injections. On postnatal day 1, pups were cross-fostered so that each mother received pups from all three treatments. Thus, nine groups (based on the prenatal and postnatal drug exposures) of adult female rats were tested in each seizure test: C/C, C/S, C/MA, S/C, S/S, S/MA, MA/C, MA/S, MA/MA. The present study demonstrated that both the excitatory NMDA system and the inhibitory GABA system are involved in the proconvulsive effect of MA during prenatal and partially also postnatal development in female rats. However, because our results did not show any improvement in seizure susceptibility in prenatally MA-exposed animals that were fostered by control mothers (MA/C) relative to their siblings fostered by MA-treated mothers (MA/MA), our hypothesis of the cross-fostering effect seems to be incorrect in contrast to our behavioral studies.