Project Summary

David Feifel, M.D., Ph.D. (Independent Investigator 2004) of University of California, San Diego, proposes studying in more detail the Brattleboro rat as a new animal model for schizophrenia. The Brattleboro rat strain has brain abnormalities due to a mutation in a single gene that regulates production of vasopressin. Dr. Feifel’s laboratory recently discovered that Brattleboro rats have deficits in prepulse inhibition (PPI) analogous to schizophrenia patients. PPI refers to the normal reduction of the startle response to a sudden intense stimulus (“pulse”) when it is preceded by a much weaker pre-stimulus (“prepulse”). PPI is thought to reflect the ability of the brain to filter extraneous environmental information. Abnormally low PPI is a consistent finding in unmedicated schizophrenia patients. His laboratory also found PPI deficits in Brattleboro rats are reversed by chronic but not acute treatment with haloperidol, a first generation antipsychotic. In contrast, clozapine, a second generation antipsychotic and PD149163, a potential novel antipsychotic with second-generation features, significantly enhance PPI in Brattleboro rats after a single dose. Chronic treatment with these drugs produced stronger effects. These preliminary findings suggest the Brattleboro rat may represent a novel animal model for studying the causes of PPI deficits exhibited in schizophrenia and for developing new treatments.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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