Modeling motivational deficits in mouse models of schizophrenia: Behavior analysis as a guide for neuroscience

In recent years it has become possible to develop animal models of psychiatric disease in genetically modified mice. While great strides have been made in the development of genetic and neurobiological tools with which to model psychiatric disease, elucidation of neural and molecular mechanisms thought to underlie behavioral phenotypes has been hindered by an inadequate analysis of behavior. This is unfortunate given the fact that the experimental analysis of behavior has created powerful methods for isolating and describing the functional properties of behavioral mechanisms that are capable of providing deep understanding of behavioral phenotypes. A better understanding of the biological basis of normal behavior and its disturbance in psychiatric disease will require the application of these rigorous behavior analytic tools to animal models. In this review we provide an example of a merging of genetic and behavioral methods and illustrate its utility in the analysis of a mouse model of the motivational deficits in schizophrenia. The synergy between basic behavior analysis, neuroscience, and animal models of psychiatric disease has great potential for achieving a deeper understanding of behavior and its neurobiological mechanisms as well as for leading to improvements in diagnosis and treatment in clinical settings.

Research highlights
► A genetically engineered mouse model of schizophrenia demonstrates a motivational impairment in the progressive ratio schedule that is analogous to the motivational deficits observed in patients.
► The phenotype is not due to motor limitations, increased satiation, increased rate of extinction, or decreased tolerance to delays between rewards.
► The behavioral analysis suggests a common psychological mechanism mediating the motivational deficit in the mouse and in individuals diagnosed with schizophrenia.