Excitatory actions of NMDA receptor antagonists in rat entorhinal cortex and cultured entorhinal cortical neurons.
J Väisänen, A M Lindén, M Lakso, G Wong, U Heinemann, E Castrén
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology July 1, 1999 DOI: 10.1016/s0893-133x(99)00006-8 via PubMed
Summary
AI-generated from the abstractNon-competitive NMDA receptor antagonists MK-801, PCP, and ketamine strongly and dose-dependently increase expression of the immediate early gene c-fos in neurons of layer III of the rat caudal entorhinal cortex. This induction is delayed and blocked by antipsychotic drugs. In cultured primary entorhinal neurons, high doses of MK-801 and PCP kill the cells without inducing c-fos, showing that the in vitro model does not fully replicate in vivo effects. These excitatory effects may be linked to the psychotropic side effects of these drugs and could serve as a model system for studying psychosis neurobiology.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rat entorhinal cortex and cultured primary entorhinal cortical neurons |
| Interventions | MK-801 PCP ketamine |
| Key finding | NMDA receptor antagonists MK-801, PCP, and ketamine produce a strong, dose-dependent increase in c-fos expression in layer III of the rat caudal entorhinal cortex, which is inhibited by antipsychotic drugs. |
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.