Glutamatergic Hypofunction

The suggestion that a glutamatergic dysfunction may be involved in the pathophysi-ology of schizophrenia was derived from the observation that when individuals came into the hospital under the influence of PCP (also known as angel dust), it was very difficult for clinicians to distinguish them from schizophrenia patients. Drugs such as PCP and ketamine function by blocking the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. Not only can these drugs mimic schizophrenia in a normal individual, they can exacerbate symptoms in patients with schizophrenia. Studies of glutamate receptors in postmortem tissue have generally found decreased binding to the kainate subtype of glutamate receptors in the hippocampus and limbic cortex, and increased binding to the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA subtypes of glutamate receptors in the prefrontal cortex (Coyle, 1996). These changes in AMPA and kainate receptor subtypes have been reproduced in microarray studies (Mirnics et al., 2001).

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