EFFECTS OF PRENATAL COCAINE EXPOSURE ON THE DEVELOPING HIPPOCAMPUS - INTRINSIC AND SYNAPTIC PHYSIOLOGY

A variety of neurological complications has been reported in infants e xposed to cocaine during gestation. In the present study, intrinsic ce ll properties of hippocampal neurons from CA1, CA3, and dentate gyrus regions were measured and compared in tissue from neonatal rats expose d to saline or cocaine in utero. Synaptic proper ties of the CA1 pyram idal cell region were analyzed at postnatal day (P) 20 with the use of extracellular and intracellular recording techniques. In vitro intrac ellular recordings (n = 223) obtained at P10, P15 and P20 in tissue fr om cocaine- and saline-exposed animals revealed no differences in stan dard cell properties such as resting membrane potential, input resista nce, time constant, and action potential amplitude or duration. Hippoc ampal slices from cocaine-exposed animals exhibited a marked reduction of spike frequency adaptation for all three types of principal hippoc ampal neurons (e.g., CA1, CA3, and granule cells). The amplitudes of a fterhyperpolarizations following a spike train were also decreased in CA1 and CA3 cells in tissue from cocaine-exposed animals. Extracellula r and intracellular recordings in the CA1 pyramidal cell region at P20 were obtained to assess and compare synaptic function in tissue from cocaine- and saline-exposed animals. In hippocampal slices from cocain e-exposed animals, synaptic responses in the CA1 region were character ized by multiple population spike activity and reduced inhibitory post synaptic potentials. The reduction in fast inhibitory postsynaptic pot ential conductance was not associated with a change in reversal potent ial. These results suggest that gestational cocaine exposure induces s ignificant changes in intrinsic and synaptic electrophysiological prop erties of hippocampal neurons in the developing animal. The cell and s ynaptic features are consistent with an increase in hippocampal excita bility, which may contribute to the neurobehavioral deficits and epile ptogenic predisposition reported in this infant population. As such, t his in utero drug exposure model may provide a useful system in which to elucidate and study the basic cellular mechanisms underlying neurol ogical complications associated with maternal cocaine abuse.