Project Summary

Morgane M. Thomsen, Ph.D. (Young Investigator 2008) of McLean Hospital/Harvard University, is examining the role of the muscarinic cholinergic receptors (mAchR's) in the pathophysiology and treatment of schizophrenia. There are five known mAchR's (M1-M5). It is unknown which of these receptors may have potential to mediate antipsychotic effects, cognitive improvements, or undesirable effects in schizophrenic patients, thus far severely limiting the usefulness of drugs acting at mAchR's. The aim of the present project is to identify individual mAchR's as potential targets for new antipsychotic drugs, either alone or as adjuvant medication that may enhance the benefits of current anti-schizophrenia therapies. Specifically it will evaluate in rodents the antipsychotic potential of selective M1- and M4-agonist drugs by testing selective agonist and antagonist toxins in the prepulse inhibition (PPI) and locomotor activity assays, both alone and in combination with known antipsychotic medications (haloperidol, clozapine). This research could contribute to the development of a novel class of antipsychotic drugs.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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