The PhD thesis of Katja Savolainen, MSc (Pharm), provides improved animal models for the assessment of novel drugs for the treatment of cognitive and negative symptoms of schizophrenia. The public examination will be held in Finnish online on 30 October 2020.
Schizophrenia is a chronic neuropsychiatric syndrome
Schizophrenia is a severely debilitating, multiform neuropsychiatric syndrome. The symptoms of schizophrenia can be divided into three main categories, namely positive, negative and cognitive, although also affective symptoms are common. The positive symptoms, better known as psychotic symptoms, include for example hallucinations and delusions. Social withdrawal, affective flattening and anhedonia are characteristic negative symptoms. The cognitive symptoms consist of a wide range of impairments in cognitive abilities, such as attention, learning, memory, and cognitive flexibility. Currently available pharmacotherapies mainly affect the positive symptoms, while there is no effective treatment for the negative and cognitive symptoms causing a loss of social and occupational functioning and reducing the quality of life. Clearly, there is a significant unmet medical need in the treatment of these symptoms.
A need for better models of cognitive and negative symptoms of schizophrenia in the development of novel drugs
One major challenge in non-clinical drug discovery has been the inadequacy of current animal models to mimic the negative and cognitive symptoms of schizophrenia. These models have a poor ability to predict the clinical efficacy of novel drugs. The general objective of this study was to develop and validate animal models mimicking the cognitive and negative symptoms of schizophrenia as a part of the assessment of the efficacy of novel drugs. Schizophrenia-like cognitive and negative symptoms were induced pharmacologically by using phencyclidine (PCP), which have been shown to induce schizophrenia-like symptoms in humans, as well as in experimental animals.
The PCP administration protocols could be adjusted in order to induce disturbances in social behavior and deficits in cognitive domains relevant to schizophrenia, i.e. problems in visual learning and memory, and deficits in cognitive flexibility, without inducing non-specific behavioral effects. Furthermore, the selection of rat strain had a significant effect on the assessment of PCP-induced cognitive deficits in a visually demanding cognitive test. A novel drug ameliorated the PCP-induced impairments in both cognitive flexibility and social interaction.
In this study, the PCP administration protocol could be adjusted to model impairments in cognitive domains and negative symptoms relevant to schizophrenia. These models may be beneficial in the testing of novel drugs to treat schizophrenia.
The doctoral dissertation of Katja Savolainen, Master of Science (Pharmacy), entitled Non-clinical modeling of cognitive and negative symptoms of schizophrenia as a part of the assessment of novel drugs, will be examined at the Faculty of Health Sciences. The Opponent in the public examination will be Docent Sanna Janhunen of the University of Helsinki, and the Custos will be Professor Markus Forsberg of the University of Eastern Finland.
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