Progression of Behavioral Deficits During Periadolescent Development Differs in Female and Male DISC1 Knockout Rats

Mutations in the disrupted in schizophrenia-1 (DISC1) gene are associated with an increased risk of developing psychological disorders including schizophrenia, bipolar disorder, and depression. Assessing the impact of knocking out genes, like DISC1, in animal models provides valuable insights into the relationship between the gene and behavioral outcomes. Previous research has relied on mouse models to assess these impacts, however these may not yield as reliable or rich a behavioral analysis as can be obtained using rats. Thus, the goal of the present study was to characterize the behavioral effects of a biallelic functional deletion of the DISC1 gene in the Sprague Dawley rat. Female and male wild type and DISC1 knockout rats were assessed beginning just prior to weaning and during the post-weaning periadolescent period. The primary outcomes evaluated were activity, anxiety, responses to novel objects and conspecifics, and prepulse inhibition. These behaviors were selected as analogous indices of psychological dysfunction in humans. The DISC1 knockout had significant effects on behavior, although the kind and magnitude of deficits was different for females and males: in females, effects included hyperactivity, aversion to novelty, and a modest prepulse inhibition deficit; in males, effects in anxiety and neophobia were mild but their prepulse inhibition deficit was large. These data confirm that the DISC1 knockout rat model is an excellent way to reproduce and study symptoms of psychological disorders and provides compelling evidence for differential consequences of its dysfunction for females and males in the progression and emergence of specific behavioral deficits.