Prenatal exposure to morphine alters kinetic properties of NMDA receptor-mediated synaptic currents in the hippocampus of rat offspring

Whole-cell patch-clamp recordings of pharmacologically isolated N-methyl-D- asparate (NMDA) receptor-mediated evoked excitatory postsynaptic currents ( EPSCs) were made, to study whether prenatal exposure to morphine affected f unctional properties of synaptic NMDA receptors in hippocampal slices of 2- week-old rat offspring from morphine-addicted mothers. The saturated amplit ude of synaptic NMDA receptor-mediated EPSCs from morphine-treated offsprin g was about twofold larger than that from vehicle-control offspring. The ap parent dissociation constant (K-d) values of NMDA receptors for Mg2+ at 0 m V were 7.5 +/- 7.4 and 7.9 +/- 1.3 mM in slices from vehicle-control and mo rphine-treated offspring, respectively. In addition, no distinguishable cha nges in the voltage-dependent nature and the reversal potential of NMDA rec eptors occurred in morphine-treated offspring, suggesting no alterations of Mg2+ blockade and ion selectivity to NMDA receptors. The 10-90% rise times of NMDA receptor-mediated EPSCs in morphine-treated offspring became longe r than those in vehicle-control offspring. The decay of NMDA receptor-media ted EPSCs in both morphine-treated and Vehicle-control offspring could be d escribed by the sum of a fast and a slow exponential function. The slow, bu t not fast, decay times of synaptic NMDA receptor-mediated currents in morp hine-treated offspring became slower than those in vehicle-control offsprin g. Collectively, these results suggest that prenatal exposure to morphine a ltered kinetic properties of synaptic NMDA receptors in hippocampal CA1 pyr amidal neurons of rat offspring during early life. The extended duration of synaptic;NMDA receptor-mediated currents presumably provided more Ca2+ ent ry through NMDA receptors in morphine-treated offspring, and its further pr olongation by depolarization in such young offspring strengthened NMDA rece ptor-dependent functions. Thus, in light of pathophysiological implications within the central nervous system of morphine-treated offspring during ear ly life, the present study may provide important insights and serve as a ba sis for therapeutic intervention in conditions under which NMDA receptors b ecome abnormal. Hippocampus 2000;10:654-662. (C) 2000 Wiley-Liss, Inc.