Posted by deniseuk190466 on November 18, 2007, at 11:59:39
I was just reading up and Ketamine and Glutamate, I don't really understand much about chemistry but I can just about understand some of the studies.
I have found two studies which seem to contradict each other, as below. One study says that Ketamine increases Glutamate, the other says that it decreases Glutamate as below. Do these people know what they are doing or is just me getting confused again?
Abstract
Previous studies have shown that the metabotropic glutamate receptor (mGluR)2/3 agonist LY354740 attenuated glutamate release in medial prefrontal cortex (mPFC) induced by the non-competitive N-methyl--aspartate (NMDA) receptor antagonist phencyclidine. In the present study we examined the effects of the more potent mGluR2/3 selective agonist LY379268 on ketamine-evoked glutamate and dopamine (DA) release in mPFC of male rats. Subjects were implanted with a unilateral microdialysis probe in the mPFC and were tested 12–24 h after implantation. Ketamine (18 mg/kg, s.c.) evoked a significant release of glutamate and DA, although the glutamate response was slower in onset compared with DA. Pretreatment with either systemic (3 mg/kg s.c.) or local (1 μM, in the probe) LY379268 blocked ketamine-evoked glutamate, but not DA, release. When applied directly to the mPFC via the dialysis probe, ketamine (1 mM in the probe) had no effect on glutamate release but did significantly enhance the release of DA. Application of NMDA (500 μM in the probe), on the other hand, decreased DA while increasing glutamate release. The effect of NMDA on evoking glutamate release was blocked by systemic but not local administration of LY379268. These findings indicate that systemic ketamine increases both glutamate and DA release in mPFC and that the effect on glutamate can be blocked by stimulating mPFC group II mGluR receptors. Local ketamine, on the other hand, does not increase glutamate but does increase DA release. This suggests that ketamine acts outside of the mPFC to enhance glutamate, but within the mPFC to enhance DA release. The origin of the ketamine effect on mPFC glutamate is currently not known.Author Keywords: microdialysis; metabotropic glutamate receptors; schizophrenia; antipsychotic; neurotransmitter release
Abbreviations: aCSF, artificial cerebrospinal fluid; ANOVA, analysis of variance; DA, dopamine; EDTA, ethylenediaminetetraacetic acid; HVA, homovanillic acid; mGluR, metabotropic glutamate receptor; MK-801, (+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclo-hepten-5,10-iminemaleate; mPFC, medial prefrontal cortex; NMDA, N-methyl--aspartate; PCP, phencyclidine; TTX, tetrodotoxin
Corresponding author. Tel: +1-858-202-5217; fax: +1-858-202-5813.
Purpose: In cerebral ischemia/anoxia, the glutamate transporter runs in reverse and releases glutamate into the extracellular space, causing irreversible neuronal damage. Intravenous anesthetics attenuate overall glutamate release and prevent neuronal injury during anoxia/ischemia, but their effect on the glutamate transporter is variable.Methods: A human glial glutamate transporter (hGLT-1) cDNA was isolated by screening a human cerebral cortical library. Cloned cDNA was transfected in Chinese hamster ovary cells. The effect of the intravenous anesthetics midazolam (0.3 to 30 µM), ketamine (10 to 100 µM), thiopental (30 to 300 µM), and propofol (3 to 30 µM) on reversed uptake of Lglutamate via hGLT-1 was examined by whole-cell patch-clamp.
Results: Midazolam at a concentration 3 µM reduced outward currents arising from reversed L-glutamate uptake via hGLT-1 in a concentration-dependent manner. While, ketamine at 100 µM attenuated the same outward currents, to 53.3 ± 11.4% of those seen in controls without anesthetics (P < 0.05, n=5). In contrast, neither thiopental nor propofol showed effects on outward currents mediated by reversed operation of hGLT-1.
Conclusions: These results suggest that midazolam and ketamine, but not thiopental and propofol, have a capacity to inhibit glutamate release via GLT-1 directly.
Denise
poster:deniseuk190466
thread:795744
URL: http://www.dr-bob.org/babble/20071115/msgs/795744.html