A greater tendency for representation mediated learning in a ketamine mouse model of schizophrenia

Representation mediated learning is a behavioral paradigm that could be used to potentially capture psychotic symptoms including hallucinations and delusions in schizophrenia. In studies of mediated learning, representations of prior experience can enter into current associations. Using a ketamine model of schizophrenia, we investigated whether mice exposed to ketamine during late adolescence subsequently showed an increased tendency to use a representation of a prior gustatory experience to form associations in learning. Mice were given prior experience of an odor and a taste presented together. The odor was subsequently presented alone with gastrointestinal illness induced by a lithium chloride injection. A consumption test was then given to assess whether the taste, despite its absence during conditioning, entered into an association with the induced illness. Such learning would be mediated via a representation of the taste activated by the odor. Our results showed that control mice displayed no aversion to the taste following the procedures just described, but mice that had been treated developmentally with ketamine exhibited a significant taste aversion, suggesting a greater propensity for mediated learning. Complementary to that finding, ketamine-exposed mice also showed a greater susceptibility to mediated extinction. Chronic treatment with the antipsychotic drug, risperidone, in ketamine-exposed mice attenuated mediated learning, a finding that may be related to its known efficacy in reducing the positive symptoms of schizophrenia. These data provide a setting with potential relevance to preclinical research on schizophrenia, to study the neural mechanisms underlying a propensity for aberrant associations and assessment of therapeutics. (PsycINFO Database Record