Affiliation:
1. Department of Zoology, University of OxfordSouth Parks Road, Oxford OX1 3SY, UK
2. Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial CollegeNorfolk Place, London W2 1PG, UK
3. Stanley Medical Research Institute5430 Grosvenor Lane, Bethesda, MD 20814-2142, USA
Abstract
With increasing pressure to understand transmissible agents, renewed recognition of infectious causation of both acute and chronic diseases is occurring. Epidemiological and neuropathological studies indicate that some cases of schizophrenia may be associated with environmental factors, such as exposure to the ubiquitous protozoan
Toxoplasma gondii
. Reasons for this include
T. gondii
's ability to establish persistent infection within the central nervous system, its ability to manipulate intermediate host behaviour, the occurrence of neurological and psychiatric symptoms in some infected individuals, and an association between infection with increased incidence of schizophrenia. Moreover, several of the medications used to treat schizophrenia and other psychiatric disease have recently been demonstrated
in vitro
to possess anti-parasitic, and in particular anti-
T. gondii
, properties. Our aim here was thus to test the hypothesis that the anti-psychotic and mood stabilizing activity of some medications may be achieved, or at least augmented, through their
in vivo
inhibition of
T. gondii
replication and invasion in infected individuals. In particular we predicted, using the epidemiologically and clinically applicable rat-
T. gondii
model system, and following a previously described and neurologically characterized ‘feline attraction’ protocol that haloperidol (an anti-psychotic used in the treatment of mental illnesses including schizophrenia) and/or valproic acid (a mood stabilizer used in the treatment of mental illnesses including schizophrenia), would be, at least, as effective in preventing the development of
T. gondii
-associated behavioural and cognitive alterations as the standard anti-
T. gondii
chemotherapeutics pyrimethamine with Dapsone. We demonstrate that, while
T. gondii
appears to alter the rats’ perception of predation risk turning their innate aversion into a ‘suicidal’ feline attraction, anti-psychotic drugs prove as efficient as anti-
T. gondii
drugs in preventing such behavioural alterations. Our results have important implications regarding the aetiology and treatment of such disorders.
Subject
General Agricultural and Biological Sciences,General Environmental Science,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine
Cited by
204 articles.
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