Schizophrenia in Translation: Dissecting Motivation in Schizophrenia and Rodents

摘要

The negative symptoms of schizophrenia include deficits in motivation, for which there is currently no treatment available. Animal models provide a powerful tool for identifying the potential pathophysiological mechanisms underlying the motivation deficits of schizophrenia with the aim of discovering novel treatment targets. The success of such an approach critically depends on meticulously detailed analysis of motivational phenotypes in patients and in animal models. Here, we review the results of recent human behavioral and imaging studies of motivation, and we relate those findings to the results from animal studies, including a mouse model of striatal dopamine D2 receptor hyperfunction. The motivational deficit in patients with schizophrenia is not due to an inability to experience pleasure in the moment as hedonic reaction appears intact in patients. Instead, the motivation deficit represents a reduced capacity for anticipating future pleasure resulting from goal-directed action. The diminished anticipation appears to be a consequence of an inability to accurately represent the expected reward values of actions. A strikingly similar phenotype in incentive motivation has also been described in mice with striatal dopamine D2 receptor hyperfunction. These convergent findings identify potential pathophysiological mechanisms that underlie the deficit in anticipatory motivation, and importantly, the mouse model provides a tool for investigating novel treatment strategies, which we discuss here.