EFFECT OF MATERNAL MAGNESIUM SULFATE ADMINISTRATION ON BRAIN CELL FUNCTION IN THE COCAINE-EXPOSED FETAL GUINEA PIG. • 429

Previous studies from our laboratory have shown that prenatal cocaine exposure alters brain cell membrane function by decreasing membrane Na⁺,K⁺-ATPase activity and potentiates the glutamate/glycine-dependent activation of the NMDA receptor. Magnesium sulfate(MgSO₄) attenuates neuronal membrane dysfunction in hypoxic newborn piglets by preserving N-methyl-D-aspartate (NMDA) receptor number and affinity, and Na⁺,K⁺-ATPase activity. Data describing the interaction of cocaine and magnesium on neuronal function are lacking. The present study tests the hypothesis that maternal MgSO₄ administration will prevent cocaine-induced NMDA receptor/ion channel modification in the fetus. Studies were performed in 6 pregnant guinea pigs (58 days gestation) assigned to 3 groups: Cocaine-treated (COC, n= 2). Magnesium-treated (MG, n=2) and Magnesium/Cocaine-treated (MG-COC, n=2). Animals in the MG and MG-COC groups received an initial bolus of MgSO₄ 300 mg/kg i.p. followed by 50 mg/kg q 30 min for 5 hours. Mean maternal [Mg⁺⁺] was 10.5 mg%. Cocaine HCl 30 mg i.p. was given to the COC and MG-COC groups one hour prior to delivery of the fetuses. ³[H]MK-801 binding studies, an index of NMDA receptor activation, were performed in a concentration range from 0.5 to 50 nM in a reaction medium containing 10mM HEPES (pH 7.0), 100 μM glutamate and glycine, and 75 μg protein. Total number of receptors (Bmax) in the COC, MG and MG-COC groups were 1.08 ± 0.13, 1.34 ± 0.07 and 1.19± 0.09 pmol/mg protein (mean±SD). Kd for the same groups were 2.64 ± 0.22, 5.18 ± 0.87 and 4.65 ± 0.01 nM. The data show that MgSO₄ may prevent the cocaine-induced increase in the affinity (decreased Kd) of the NMDA receptor for ³[H]MK-801 in fetal brains. We speculate that cocaine-induced modification of the NMDA receptor ion/channel complex may alter NMDA-mediated developmental processes that are essential for fetal brain function. Furthermore, administration of MgSO₄ to cocaine-exposed fetuses may attenuate neurotoxicity by the glutamate-type NMDA receptor in the developing fetal brain. (Funded by NIH-HD-20337, MOD#6- FY94-0135, UCPR 506-93)