Behavioural and pharmacological study of an animal model relevant to schizophrenia

Abstract

Schizophrenia is a chronic, common and debilitating illness which causes serious psychosocial impairments. Despite the adverse impact of schizophrenia on public health, progress in understanding its pathophysiology is frustratingly slow, which hinders discovery of new therapeutic mechanisms. The major factors that have impeded this exploration are the complex neurobiology of higher brain function and the ethical and practical difficulties of investigating the living brain. Thus, animal models are useful to investigate the pathophysiology and therapeutics of schizophrenia and related conditions.

A useful animal model is an important tool to illuminate pathophysiology and signpost a target for treatment development. But animal models also have limitations and not all the phenotypic traits thought relevant to schizophrenia are expressed in all models. However, in-bred mouse strains have proved useful in the field of research into neurodevelopmental disorders. Therefore, in the first part of this thesis, behavioural and protein expression of C57BL/6N and 129 X1/SvJ mice were compared. The 129X1/SvJ strain, like the C57BL/6N strain, is a widely used background strain for behavioral research. Both 129X1/SvJ and C57BL/6N are routinely used in gene-targeting research. The results suggested that C57BL/6N mice mimic aspects of schizophrenia, at least in comparison with 129X1/SvJ mice. Therefore C57BL/6N mouse may have application in pre-translational screening of new treatments for schizophrenia.

Oxytocin has been proposed as a possible treatment for neurodevelopmental conditions such as schizophrenia. However, there are gaps in the understanding of its therapeutic potential, in particular the extent to which it may have effects on non-social as well as social behaviors in both sexes. In the second part of the thesis, female and male C57BL/6N mice were used to study the effects of oxytocin on social and non-social behaviours relevant to schizophrenia. Oxytocin generally ‘improved’ behaviours analogous to those reported to be impaired in neurodevelopmental disorders, but effects were observed at different doses in each sex. The work here suggests oxytocin has potential for treatment of both social and non-social features of schizophrenia.

Further research into the clinical application of this peptide hormone, which may in turn significantly extend treatment options across a spectrum of neurodevelopmental conditions, should be encouraged.