Posted by JohnX on October 13, 2001, at 14:59:30
using an NMDA antagonists to inhibit CRF
release? Potential in difficult to treat
depression particularly associated with PTSD?
Brainstorming..had a feeling I might find
a reference to this (of course I probably cound
find a theory for anything if I searched far
enough).Other random blurbs (related to NMDA stuffy):
- Some people develop reverse tolerance to
stimulants (the stimulant gains strength over
time potentially leading ultimately to psychosis).
- Other people (me) develop rapid tolerance.Could there be a correlation link between types of
tolerance and responses to stimulants to how the
HPA axis works? NMDA receptor antagonists shown
to inhibit tolerance and sensitization to stims and
opiods.Tboughts?
-John
Peptides 1999;20(1):93-100 (ISSN: 0196-9781)
Cratty MS; Birkle DL [Find other articles with these Authors]
Department of Pharmacology and Toxicology, West Virginia University, Robert C. Byrd Health Sciences Center, Morgantown 26506, USA.Corticotropin-releasing factor (CRF) plays an important role in the activation of centrally mediated responses to stress. The amygdala, a limbic structure involved in the stress
response, has a significant number of CRF cell bodies and CRF receptors. Activation of glutamatergic projections to the amygdala has been implicated in the stress response.
Few studies have evaluated neurotransmitter-stimulated CRF release in the amygdala. We measured the effects of glutamate (0.1-1000 microM) and N-methyl-D-aspartate
(NMDA, 0.1-1000 microM) on CRF release from the amygdala using primary neuronal cultures from embryonic rat brains (E18-19). Experiments were performed after the
cultures grew for 17-20 days. CRF was measured using radioimmunoassay. The excitatory amino acid neurotransmitters, glutamate and NMDA, stimulated CRF release in a
concentration-dependent manner. The apparent EC50 values for glutamate and NMDA were 17.5 microM and 12 microM, respectively. Consistent with a NMDA
receptor-driven event, glutamate-stimulated CRF release was blocked by the NMDA antagonist, 2-amino-5-phosphonovaleric acid (AP-5, 1-100 microM) and antagonized by
the addition of 1.2 mM MgCl2 to the incubation medium. These results implicate an inhibition of CRF release in the amygdala as a possible mechanism for the reported
anxiolytic effects of NMDA antagonists.
poster:JohnX
thread:81210
URL: http://www.dr-bob.org/babble/20011007/msgs/81210.html