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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rat entorhinal cortex and cultured primary entorhinal cortical neurons |
| Interventions | MK-801 PCP ketamine |
| Key findings | 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.