Long term antipsychotic treatment does not alter metabolite concentrations in rat striatum: an in vivo magnetic resonance spectroscopy study

Abstract

Proton magnetic resonance spectroscopy (MRS) studies of schizophrenic patients generally reveal reduced levels of N-acetyl aspartate (NAA) when compared with healthy controls. Whether this reduction is due to the disease or to the drugs used for treatment remains an open question. Numerous human and animal studies have attempted to determine the effects of antipsychotics on NAA levels with mixed results. The majority of the animal studies were ex vivo, which may not accurately reflect the in vivo situation, and limitations of the human studies include previous or concomitant medications or other confounds. To overcome these limitations, we dosed 10 rats/group for six months via drinking water with 0.2 or 2 mg/kg/day haloperidol or 10 or 30 mg/kg/day clozapine. Control rats received unadulterated water. Proton MRS data were collected longitudinally over the six month period from a 64 μL voxel containing primarily the right striatum prior to and monthly during drug administration and used to estimate the concentrations of NAA, creatine, and choline. Ratios of NAA, choline, inositol and glutamate+glutamine to creatine were also calculated. Only the Cho/Cr ratio showed a significant time-by-treatment effect (p=0.0285). These results are in agreement with previous studies of the striatum. However, regional and disease-specific effects remain unresolved.

Figure 1

Representative MR data from a control rat. A) Voxel location in right striatum. LCModel fits to the spectra from months B) 0, C) 1, D) 2, E) 3, F) 4, G) 5, and H) 6.

Figure 2

Monthly concentration estimates in institutional units for each treatment group. CH: 30 mg/kg/day clozapine; CL: 10 mg/kg/day clozapine; HH: 2 mg/kg/day haloperidol; HL: 0.2 mg/kg/day haloperidol; S: control.

Figure 3

Monthly ratios for each of the treatment groups. CH: 30 mg/kg/day clozapine; CL: 10 mg/kg/day clozapine; HH: 2 mg/kg/day haloperidol; HL: 0.2 mg/kg/day haloperidol; S: control.