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

Bustillo, Juan; Wolff, Christina; Myers-y-Gutierrez, Adan; Dettmer, Todd S.; Cooper, Tom B.; Allan, Andrea; Lauriello, John; Valenzuela, C.Fernando

doi:10.1016/S0920-9964(02)00528-5

« Previous Next »Schizophrenia Research
Volume 66, Issue 1 , Pages 31-39, 1 January 2004

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

Juan Bustillo
- Department of Psychiatry, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
- Department of Neurosciences, University of New Mexico Health Sciences Center, Basic Medical Sciences Building, Room 145, Albuquerque, NM 87131, USA
- Financial support: State of New Mexico Antipsychotic Algorithm Project Consultation Grant from New Mexico Department of Health.
- Financial support: Mental Illness Neuroscience Discovery Institute.
Christina Wolff
- Department of Psychiatry, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
Adan Myers-y-Gutierrez
- Mental Illness Neuroscience Discovery Institute, USA
Todd S. Dettmer
- Department of Neurosciences, University of New Mexico Health Sciences Center, Basic Medical Sciences Building, Room 145, Albuquerque, NM 87131, USA
- Financial support: UNM-Minority Biomedical Research Support Program funded by NIH Grant R25 GM 60201-2.
Tom B. Cooper
- Nathan Kline Institute, USA
- College of P&S Columbia University, USA
Andrea Allan
- Department of Neurosciences, University of New Mexico Health Sciences Center, Basic Medical Sciences Building, Room 145, Albuquerque, NM 87131, USA
John Lauriello
- Department of Psychiatry, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
- Financial support: State of New Mexico Antipsychotic Algorithm Project Consultation Grant from New Mexico Department of Health.
C.Fernando Valenzuela
- Corresponding author. Tel.: +1-505-272-3128; fax: +1-505-272-8082.
- Department of Neurosciences, University of New Mexico Health Sciences Center, Basic Medical Sciences Building, Room 145, Albuquerque, NM 87131, USA
- Financial support: NIH Grants MH63126 and AA12684.

Received 6 June 2002; received in revised form 2 December 2002; accepted 12 December 2002.

Abstract

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.