Altered exploration and sensorimotor gating of the chakragati mouse model of schizophrenia.
Schizophrenia is a prevalent neurodevelopmental psychiatric disorder with poor prognosis and limited understanding of its etiology. This limited etiological understanding renders developing animal models of schizophrenia difficult. Although attempts are made to recreate putative etiologies in models, these models may only enable the generation of treatments targeted at the mechanisms manipulated. Although the chakragati mouse was not created as a result of a specific gene target, reports to date suggest these mice exhibit behavioral abnormalities that are consistent with some observed in patients with schizophrenia. As an initial screen on the relevance of these mice to schizophrenia, we tested the exploration and sensorimotor gating of male and female chakragati mice in the cross-species tests behavioral pattern monitor (BPM) and prepulse inhibition (PPI), respectively. The chakragati mice exhibited hyperactive yet more meandering/circling movements of exploration compared with wildtype (WT) littermates. Moreover, chakragati mice exhibited impaired PPI compared with WT mice, primarily at high prepulse intensity levels. Thus, chakragati mice share some of the abnormal exploratory and PPI behaviors that are observed in patients with schizophrenia. These behaviors can be used to screen for novel antipsychotics which may be based on novel mechanisms of action. The multivariate abnormal exploration of these mice may also yield further information for treatment effects. Further characterization of these mice in tasks with putative links to negative or cognitive symptoms may further advance the utility of these mice as a screen for novel treatments for schizophrenia.
Department of Psychiatry, University of California San Diego.
Jared W
JW
Young
Chakra Biotech Pte Ltd.
Anil
A
Ratty
Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System.
Gavin S
GS
Dawe
Department of Psychiatry, University of California San Diego.
Mark A
MA
Geyer
D000818:Animals; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D065808:Prepulse Inhibition / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D012565:Schizophrenic Psychology; D012737:Sex Factors