So we all should know one hypothesis of schizophrenia is low NMDA-activity (or NMDA hypoactivity) - this is because NMDA helps to filter dopamine in the brain and shuffle it into the correct area's, low NMDA leads to a significant change in DAT (Dopamine Transporter) and low calcium channel activity that leads to disturbing personality changes, ahedonia/dysphoria can be possible, DEpersonalization and delirium, along with other classic low glutamate symptoms such as Insomnia, Fatigue etc ...and feeling like people are reading your thoughts, usually coupled with paranoia.
But you see, NMDA is the most important glutamate receptor and carries the widest range of physiological and psychotropic effects.
It also is a major signaling conductor and cross-talks with histamine.
Super HIGH NMDA has not really been studied without the presence of glutamate at other receptors, but I highly doubt that NMDA itself (and studies are lacking as well) can cause any excitotoxicity ALONE.
However, in the presence of glutamate binding at other receptors that are mostly excitory (with the exception of two metabotropic Glut receptors), there is a potential for ultimate calcification and destruction of brain neurons and myelin sheaths. Also a notable reduction in BDNF would be there.
NMDA can also enhance GABA release and releases pregnenolone and IGF-1; which can have pro-anabolic effects altogether, AND, NMDA acts as a major gonadotropic signaler, where it can massively increase testosterone and other sex hormones.
However, NMDA ALSO activates aromatase...leading to more estrogen production..
http://area1255.blog...a-receptor.html
http://www.ncbi.nlm..../pubmed/9751147
http://apt.rcpsych.org/content/8/3/189.full
http://www.ncbi.nlm....les/PMC3677126/
Most likely, NMDA enhances GABA release to short-circuit it's own actions to an extent or to trigger homeostasis in cross talk.
GABA-A antagonists will enhance NMDA-stimulated neurosteroid synthesis. As well as gonadotropin.
Edited by Area-1255, 29 August 2014 - 02:40 AM.