Grant: Operating Grant

The prevalence of smoking and nicotine dependence in schizophrenia is 3 times higher than in the general population. It has been estimated that high levels of smoking contribute significantly to the 20 % earlier mortality rate in individuals with schizophrenia. Two major theories of schizophrenia are that it involves overactivity of the neurotransmitter dopamine, or underactivatity of the neurotransmitter glutamate. Two animal models that reproduce these neurochemical states, as well as the behavioural phenotypes of schizophrenia have been developed. We will use these models to attempt to understand why people with schizophrenia smoke. Firstly, we will use these models to assess whether the neurochemical states associated with schizophrenia convey a vulnerability to addiction. Secondly we will examine whether the cognitive deficits associated with schizophrenia (and reproduced in the animal models) are improved by nicotine. Thus, these experiments will examine whether people with schizophrenia smoke as a form of self-medication to improve attentional capacity, and possibly other cognitive processes. Finally we will determine whether two different antipsychotic drugs (haloperidol and clozapine) influence nicotine self-administration and reinstatement. Understanding the reasons for the high rate of smoking could help devise better smoking cessation programs for this vulnerable population, and potentially shed light on mechanisms involved in schizophrenia.