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.
Bustillo
Juan
J
Department of Psychiatry, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Wolff
Christina
C
Myers-y-Gutierrez
Adan
A
Dettmer
Todd S
TS
Cooper
Tom B
TB
Allan
Andrea
A
Lauriello
John
J
Valenzuela
C Fernando
CF
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*; D001921:Brain / Q000187:drug effects*; D001931:Brain Mapping; D002470:Cell Survival / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003024:Clozapine / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D014150:Antipsychotic Agents; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003024:Clozapine; D006220:Haloperidol