Skip to main content
eScholarship
Open Access Publications from the University of California

UC Irvine

UC Irvine Previously Published Works bannerUC Irvine

A Methionine-Induced Animal Model of Schizophrenia: Face and Predictive Validity.

  • Author(s): Wang, Lien
  • Alachkar, Amal
  • Sanathara, Nayna
  • Belluzzi, James D
  • Wang, Zhiwei
  • Civelli, Olivier
  • et al.
Abstract

Background

Modulating the methylation process induces broad biochemical changes, some of which may be involved in schizophrenia. Methylation is in particular central to epigenesis, which is also recognized as a factor in the etiology of schizophrenia. Because methionine administration to patients with schizophrenia has been reported to exacerbate their psychotic symptoms and because mice treated with methionine exhibited social deficits and prepulse inhibition impairment, we investigated whether methionine administration could lead to behavioral changes that reflect schizophrenic symptoms in mice.

Methods

l-Methionine was administered to mice twice a day for 7 days.

Results

We found that this treatment induces behavioral responses that reflect the 3 types of schizophrenia-like symptoms (positive, negative, or cognitive deficits) as monitored in a battery of behavioral assays (locomotion, stereotypy, social interaction, forced swimming, prepulse inhibition, novel object recognition, and inhibitory avoidance). Moreover, these responses were differentially reversed by typical haloperidol and atypical clozapine antipsychotics in ways that parallel their effects in schizophrenics.

Conclusion

We thus propose the l-methionine treatment as an animal model recapitulating several symptoms of schizophrenia. We have established the face and predictive validity for this model. Our model relies on an essential natural amino acid and on an intervention that is relatively simple and time effective and may offer an additional tool for assessing novel antipsychotics.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View