The Self-medication Hypothesis in Schizophrenia: What Have We Learned from Animal Models?
There is a high prevalence of substance use and substance use disorder in patients with schizophrenia, compared with control subjects. A number of theories have been proposed to explain the high prevalence of substance use among schizophrenics. The main theories are the addiction vulnerability hypothesis, the antipsychotic-induced vulnerability hypothesis and the self-medication hypothesis. In this chapter we cover the data evaluating the self-medication hypothesis using an animal model perspective. We cover tobacco and cannabis, which are the two most important drugs for this hypothesis. First, we describe the clinical aspects and the animal models of schizophrenia that have been used to test the self-medication hypothesis. The animal literature is then introduced. From these studies, it appears that there is some support for the addiction vulnerability hypothesis for nicotine, but there is limited support for the self-medication hypothesis with nicotine. For cannabinoid agonists, there are no data covering the addiction vulnerability hypothesis. There is a clear detrimental effect of cannabinoid agonists on cognition, but, surprisingly, some studies suggest that cannabinoid agonists may improve some measures of cognition in models of schizophrenia. All those interpretations should be considered to be preliminary, due to the limited work that has been conducted so far testing these hypotheses directly. However, this does present novel strategies to correct the cognitive dysfunction associated with schizophrenia, and these warrant further exploration using both preclinical and clinical approaches.