Abstract
We have characterized excitatory effects of non-competitive NMDA receptor antagonists MK-801, PCP, and ketamine in the rat entorhinal cortex and in cultured primary entorhinal cortical neurons using expression of immediate early gene c-fos as an indicator. NMDA receptor antagonists produced a strong and dose-dependent increase in c-fos mRNA and protein expression confined to neurons in the layer III of the caudal entorhinal cortex. Induction of c-fos mRNA is delayed and it is inhibited by antipsychotic drugs. Cultured entorhinal neurons are killed by high doses of MK-801 and PCP but c-fos expression is not induced in these neurons indicating that this in vitro model does not fully replicate the in vivo effects of PCP-like drugs in the entorhinal cortex. Excitatory effects of the NMDA receptor antagonists may be connected with the psychotropic side effects of these drugs and might become a useful model system to investigate neurobiology of psychosis.
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Acknowledgements
We are grateful to Dr. J. Koistinaho for the c-fos plasmid, and to Drs. J.W. Olney, N.R. Farber, and A. Pitkänen for helpful discussions. This work was supported by grants provided by Academy of Finland and Sigrid Juselius Foundation.
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Väisänen, J., Lindén, AM., Lakso, M. et al. Excitatory Actions of NMDA Receptor Antagonists in Rat Entorhinal Cortex and Cultured Entorhinal Cortical Neurons. Neuropsychopharmacol 21, 137–146 (1999). https://doi.org/10.1016/S0893-133X(99)00006-8
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DOI: https://doi.org/10.1016/S0893-133X(99)00006-8
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