In humans as in animals, an acute hypofunctional NMDAR state is associated with increased glutamatergic activity in the anterior cingulate.

Proton magnetic resonance spectroscopy ( 1 H-MRS) studies of schizophrenia suggest an effect of the disease or of antipsychotic medications on brain N-acetyl aspartate (NAA), a marker of neuronal viability. We studied in rat the effect of haloperidol on NAA, glutamate, and glutamine in several brain regions where metabolite reductions have been reported in chronically medicated patients with schizophrenia. Two groups of 16 rats each were treated with haloperidol depo (38 mg/kg/month) and vehicle for 6 months and were killed. Concentrations of metabolites were determined by high-resolution magic angle proton magnetic resonance spectroscopy (HR-MAS 1 H-MRS) at 11.7 T in ex-vivo punch biopsies from the following brain regions: medial frontal and cingulate cortex, striatum, nucleus accumbens, dorsal and ventral hippocampus, amygdala, and temporal cortex. Factorial ANOVA of NAA concentrations revealed no significant effect of drug group (F(1,212) ¼ 1.5; p ¼ 0.22) or a group by brain region interaction (F(7,212) ¼ 1.0; p ¼ 0.43). There was a significant main effect of region (F(7,212) ¼ 17.8; po0.001) with lower NAA in the striatum. A prolonged exposure to the dopamine D2 receptor blockade effects of haloperidol does not result in changes in NAA, glutamate, glutamine, and other metabolites in the proton spectrum. These results are consistent with the only other two studies of the effect of antipsychotic drugs on NAA in the rat brain. The documented lower NAA in chronically treated schizophrenia patients is most likely not a simple effect of antipsychotic medications.

Proton magnetic resonance spectroscopy ( 1 H-MRS) is a technique for the assay of brain neurochemistry in vivo. N-acetylaspartate (NAA), the most prominent metabolite visible within the 1 H-MRS spectrum, is found primarily within neurons. The current study was designed to further elucidate NAA-cognition relationships, particularly whether such relationships are moderated by sex, or tissue type (gray or white matter). We administered standard measures of intelligence to 63 young, healthy subjects and obtained spectroscopic imaging data within a slab of tissue superior to the lateral ventricles. We found that lower NAA within right anterior gray matter predicted better performance VIQ (F=6.83, p=.011, r 2 =.10), while higher NAA within the right posterior gray matter region predicted better PIQ (F=8.175, p=.006, r 2 =.12). These findings add to the small but growing body of literature linking brain biochemistry to intelligence in normal healthy subjects using 1 H-MRSI.

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