Dopaminergic Hyperactivity Accompanied by Hyperlocomotion in C57BL/6J-bgJ/bgJ (beige-J) Mice

Abstract

Short CommunicationThe analysis of the effects of drugs on locomotor activity in rodents is an important tool in behavioral pharmacology, and changes in this parameter can have important consequences for more specific processes such as in a psychotic state (e.g., schizophrenia). In fact, activation of the mesolimbic dopaminergic system induces several behavioral changes including an increase in locomotor activity in rodents (1, 2). Furthermore, psychostimulant-induced hyperlocomotion, which is mediated by activation of the mesolimbic dopaminergic system, has been used as an animal model of schizophrenia (3). Psychotic episodes of schizophrenia have been traditionally treated by antipsychotics. Therefore, it is believed that activation of dopamine D 2 receptors, particularly in the nucleus accumbens (a terminal region of the mesolimbic dopaminergic system), is linked to episodes of schizophrenia (4). However, the pathophysiological mechanism that underlies schizophrenia, especially the etiological mechanism, is not fully understood.Genetic and environmental factors play a role in the development of schizophrenia. In animals, genetic and environmental factors can affect schizophrenia-like pathogenesis and pathophysiological changes (5). The C57BL/6J-bg J bg J (beige-J) strain of mouse originated as a spontaneous mutation from C57BL/6J lines and is of particular interest as a homologue of Chediak-Higashi syndrome in humans (6). Even though limited information is available on which molecules have been changed in the pathophysiological changes in beige-J mice, these mice show defects in lysosome-containing cells, neutral protease activity in polymorphonuclear leukocytes, and other immunological functions, especially natural killer (NK) cell functions (7 -9). A large and growing body of evidence supports the notion that immune dysfunction may play a role in schizophrenia, whereas the involvement of NK cell activities in schizophrenic patients is still controversial (10). Our preliminary study showed that beige-J mice exhibited increased locomotor activity. Therefore, we hypothesized here that dopaminergic functions in the beige-J mouse strain would be different from those in other strains. Thus, the aim of the present study was to investigate locomotor activity accompanied by activation of the dopaminergic system in beige-J mice. Previous studies have indicated that morphineinduced antinociception in beige-J (11) or diabetic (12) mice was enhanced by splenectomy. Furthermore, the hyperactivity of diabetic mice was normalized by splenec tomy (13). Therefore, the effects of splenectomy on increased locomotor activity in beige-J mice were also investigated.Male beige-J mice (National Institute on Genetics, Pharmacy and Pharmaceutical Sciences, Tokyo 142-8501, Japan Received February 25, 2014; Accepted April 14, 2014 Abstract. Genetic factors affect locomotor activity, which mainly depends on the activation of dopaminergic systems. C57BL/6J-bg J bg J (beige-J) mice, which exhibit deficiencies in immunological functi...