Neuropsychopharmacology. 1999 Jul;21(1):137-46. Related Articles, Links


Excitatory actions of NMDA receptor antagonists in rat entorhinal cortex and cultured entorhinal cortical neurons.

Vaisanen J, Linden AM, Lakso M, Wong G, Heinemann U, Castren E.

A.I. Virtanen Institute, University of Kuopio, Finland.

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.

That's a bit misleading isn't it. I was expecting some electrophysiology, but instead c-fos...

cfos mRNA and protein expression is probably the best way we have today for globally mapping neuronal activity at single-cell resolution. With electrophysiology, you're limited to whatever cells you record from, though you get superior temporal information. With cfos mapping, you compromise on the temporal dimension but make up for it by obtaining a global map of neuronal activity at single-cell res.

Too bad NMDA Antagonists are just weird feeling useless drugs

I don't completely buy the whole c-fos = excitation thing... I don't really see why anyone does. Maybe you could fill me in?

Memantine is one of the very few NMDA antagonist drugs shown clinically effective for moderate to severe Alzheimer disease (1) and Vascular Dementia (2).

May be of some benefit for Parkinson's Disease (5) and possibly for mild cognitive impairment (6).

But it would appear to impair learning in healthy humans [at least at the doses used in the studies....lower does may prove effective for improving cognition] (3) and is not effective for depression (4).


Below studies cited from Medline.

1. Arch Neurol. 2006 Jan;63(1):49-54.
2. Int Psychogeriatr. 2003;15 Suppl 1:207-13.
3. BMC Neurosci. 2005 May 12;6(1):35., Learn Mem. 2001 Jan-Feb;8(1):20-5.
4. Am J Psychiatry. 2006 Jan;163(1):153-5.
5. Clin Neuropharmacol. 1999 Sep-Oct;22(5):273-6., Arzneimittelforschung. 1977 Jul;27(7):1487-9., Dtsch Med Wochenschr. 1984 Jun 22;109(25):987-90.
6. Pharmacopsychiatry. 1988 May;21(3):144-6., Neuropsychobiology. 1996;33(1):32-40.