Treatment of rats with antipsychotic drugs: lack of an effect on brain N-acetyl aspartate levels

BACKGROUND: Proton magnetic resonance spectroscopy (1H-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 the rat the effect of antipsychotic drugs on NAA in several brain regions where NAA reductions have been reported in chronically medicated patients with schizophrenia. METHODS: Three groups of nine rats each were treated with haloperidol (6 mg/kg/day), clozapine (70 mg/kg/day) and vehicle for 6 weeks and were sacrificed. Concentrations of NAA were determined by high-performance liquid chromatography (HPLC) from the following brain regions: cortex, striatum, thalamus, hippocampus and cerebellum. RESULTS: Mixed-factorial ANOVA of NAA concentrations revealed no significant effect of drug group [F(2, 24) = 0.034; p = 0.966] or a group by brain region interaction [F(8, 44) = 0.841; p = 0.572]. There was a significant main effect of region [F(4, 21) = 6.104; p = 0.002] with higher NAA in the cortex. CONCLUSIONS: These results are consistent with the only other study of the effect of typical and atypical antipsychotic drugs on NAA in the rat brain. The well-documented lower NAA in chronically treated schizophrenia patients is probably not a simple effect of antipsychotic medications.