Behavioral phenotypes in schizophrenic animal models with multiple combinations of genetic and environmental factors

J Pharmacol Sci. 2013;121(3):185-91. doi: 10.1254/jphs.12r15cp. Epub 2013 Mar 1.

Abstract

Schizophrenia is a multifactorial psychiatric disorder in which both genetic and environmental factors play a role. Genetic [e.g., Disrupted-in-schizophrenia 1 (DISC1), Neuregulin-1 (NRG1)] and environmental factors (e.g., maternal viral infection, obstetric complications, social stress) may act during the developmental period to increase the incidence of schizophrenia. In animal models, interactions between susceptibility genes and the environment can be controlled in ways not possible in humans; therefore, such models are useful for investigating interactions between or within factors in the pathogenesis and pathophysiology of schizophrenia. We provide an overview of schizophrenic animal models investigating interactions between or within factors. First, we reviewed gene-environment interaction animal models, in which schizophrenic candidate gene mutant mice were subjected to perinatal immune activation or adolescent stress. Next, environment-environment interaction animal models, in which mice were subjected to a combination of perinatal immune activation and adolescent administration of drugs, were described. These animal models showed interaction between or within factors; behavioral changes, which were obscured by each factor, were marked by interaction of factors and vice versa. Appropriate behavioral approaches with such models will be invaluable for translational research on novel compounds, and also for providing insight into the pathogenesis and pathophysiology of schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenylyl Cyclases
  • Animals
  • Behavior, Animal*
  • Disease Models, Animal
  • Gene-Environment Interaction*
  • Humans
  • Mice
  • Nerve Tissue Proteins*
  • Neuregulin-1*
  • Nuclear Receptor Subfamily 4, Group A, Member 2 / genetics
  • Peptides
  • Phencyclidine / adverse effects
  • Phenotype
  • Point Mutation
  • Schizophrenia / etiology*
  • Schizophrenia / genetics
  • Schizophrenic Psychology*

Substances

  • Disc1 protein, mouse
  • Nerve Tissue Proteins
  • Neuregulin-1
  • Nr4a2 protein, mouse
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Peptides
  • Adenylyl Cyclases
  • Phencyclidine