Abstract
The use of animal models for the study of psychosis and new treatment development is inadequate in assessing target psychotic symptoms because animals lack an ability to use language. Despite this deficiency, new antidopaminergic antipsychotic drugs have still become available. However, even these new antipsychotics, although substantially better than the conventional compounds, do not “cure” psychosis or normalize schizophrenic symptoms. The need for new treatment strategies is apparent. The value of a human model, where language is available to describe target symptoms, is clear. Currently, there is an opportunity to use the mild psychotomimetic symptoms induced by a minimal dose of ketamine in normal humans as a model of psychosis. The mental symptoms in this model resemble some of the symptoms of schizophrenia, suggesting the additional possibility that parallel mechanisms of psychosis may occur in schizophrenia and in a ketamine state, creating a potentially viable psychosis model for pathophysiology. This paper includes arguments in support of this human model's application. Several potential outcome measures that can be used to evaluate potentially novel antipsychotics are described. This model has the potential for identifying novel therapeutics because it does not primarily utilize the dopaminergic system. Further delineation of ketamine pharmacology in humans is pivotal to the eventual application of this ketamine model in drug development.
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Lahti, A., Holcomb, H., Gao, XM. et al. NMDA-Sensitive Glutamate Antagonism: A Human Model for Psychosis. Neuropsychopharmacol 21 (Suppl 2), S158–S169 (1999). https://doi.org/10.1016/S0893-133X(99)00132-3
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DOI: https://doi.org/10.1016/S0893-133X(99)00132-3
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