NMDA receptor responses in adult hippocampal CA1 region after neonatal treatment with MK-801: comparison with NMDA receptor responses in the immature rat

Abstract Neonatal MK-801 treatment from postnatal day 8–19 leads to long-term effects on brain function, suggesting that exposure to this drug leads to the development of a brain with immature network properties. One aspect of this hypothesis, that the NMDA receptors preserve their immature state after the treatment, has been tested by measuring the potency of the competitive antagonist D-AP5 in hippocampal slices. We have previously shown that an increased potency to D-AP5 is a characteristic property of NMDA receptors during early life. In the present study we measured field potentials in the CA1 region of rat hippocampal slices evoked by iontophoretic NMDA application in the Schaffer-commissural synaptic fields. Agonist dose-response curves were constructed, followed by bath applications of increasing concentrations of the antagonist D-AP5. The maximum NMDA evoked field response was the same in slices of mature control (PND70–90; 18.9±1.2mV ) and MK-801 treated rats (PND70–90; 19.3±0.9mV ), but significantly larger in immature slices (PND10–16; 24.0±0.6mV ). The sensitivity to NMDA in hippocampal slices from each group was estimated by quantifying the iontophoretic ejection current ( =dose ) which evoked 50% of the maximum field response (EC 50 ). A significantly higher sensitivity to NMDA was found in hippocampal slices obtained from MK-801-treated rats ( EC 50 = 3.6±0.2nA ) than in slices from control ( EC 50 = 6.1±0.7nA ) or immature ( EC 50 = 5.9±0.5nA ) animals. Although these results suggest that neonatal MK-801 treatment can lead to an altered NMDA response, a pharmacological property seen to characterize an immature NMDA-receptor response is not maintained.