Glutamate related metabolism in animal models of schizophrenia

Glutamate-induced neurotoxicity plays an important role in neurological and psychiatric diseases. Thus, much attention has been given to thepotential neuroprotective role of glutamate receptor antagonists, especially to those acting on the N-methyl-D-aspartate (NMDA) subtype.However, in addition to their neuroprotective potential, these compounds have also neurotoxic and psychotogenic properties. In the present studywe used repeated injections of MK801 to examine if this non-competitive NMDA receptor antagonist could be used to produce schizophrenia-likealterations in behavior and brain metabolism in animals. Rats were given injections of MK801 (0.1 mg/kg) on six consecutive days, the last dosetogether with[1-C]glucose and [1,2-C]acetate, to probe neuronal and astrocytic metabolism, respectively. Analyses of extracts from parts of thefrontal cortex plus cingulate and retrosplenial cortices and temporal lobes were performed usingC and H magnetic resonance spectroscopy.Changes in glutamate and glutamine were restricted to the temporal lobe, in which amounts and labeling from [1-C]glucose and [1,2-C]acetatewere increased compared to control. Locomotor activity was slightly higher in rats treated with MK801 compared to untreated animals. Metabolicchanges did not resemble the alterations occurring in schizophrenia and those after repeated high dose (0.5 mg/kg) [Kondziella, D., Brenner, E.,Eyjolfsson, E.M., Markinhuhta, K.R., Carlsson, M., Sonnewald, U., 2005. Glial–neuronal interactions are impaired in the schizophrenia model ofrepeated MK801 exposure. Neuropsychopharmacology, Epub ahead of print] but rather those caused by MK801 seen after a single high dose(0.5 mg/kg) [Brenner, E., Kondziella, D., Haberg, A., Sonnewald, U., 2005. Impaired glutamine metabolism in NMDA receptor hypofunctioninduced by MK801. J. Neurochem. 94, 1594–1603.].# 2006 Elsevier Ltd. All rights reserved.