Posted by Michael Bell on November 22, 2008, at 19:22:34
In reply to Evidence of Glutamate dysfunction in SP, posted by Michael Bell on November 22, 2008, at 19:13:53
Dopamine dysfunction in the striatum has been established by studies showing DECREASED binding potential of dopamine RECEPTORS in the striatum, and INCREASED binding potential of dopamine TRANSPORTER in the striatum. This seems to point to reduced dopamine levels in the striatum (for the chemically inclined out there, please correct me if I am wrong). Anyway, Glutamate inhibits dopamine release in the striatum, leading me to believe that if people with social phobia have reduce dopamine release in the striatum, a cause of this could be the abnormally high glutamate levels that exist in their brains. Here is a study that says that glutamate regulates dopamine release in the striatum:
How glutamate regulates dopamine (DA) release in striatum has been a controversial issue. Here, we resolve this by showing that glutamate, acting at AMPA receptors, inhibits DA release by a nonclassic mechanism mediated by hydrogen peroxide (H2O2). Moreover, we show that GABAA-receptor activation opposes this process, thereby enhancing DA release. The influence of glutamate and GABA on DA release was assessed in striatal slices using carbon-fiber microelectrodes and fast-scan cyclic voltammetry. Modulation by both transmitters was prevented by H2O2-metabolizing enzymes. In addition, the influence of GABAA-receptor activation was lost when AMPA receptors were blocked with GYKI-52466. Together, these data show that modulation of DA release by glutamate and GABA depends on H2O2 generated downstream from AMPA receptors. This is the first evidence that endogenous glutamate can lead to the generation of reactive oxygen species under physiological conditions. We also show that inhibition of DA release by H2O2 is mediated by sulfonylurea-sensitive K+ channels: tolbutamide blocked DA modulation by glutamate and by GABA. The absence of ionotropic glutamate or GABA receptors on DA terminals indicates that modulatory H2O2 is generated in non-DA cells. Thus, in addition to its known excitatory actions in striatum, glutamate mediates inhibition by generating H2O2 that must diffuse from postsynaptic sites to inhibit presynaptic DA release via K+-channel opening. These findings have significant implications not only for normal striatal function but also for understanding disease states that involve DA and oxidative stress, including disorders as diverse as Parkinson's disease and schizophrenia.
poster:Michael Bell
thread:864755
URL: http://www.dr-bob.org/babble/20081114/msgs/864759.html