Project Summary

Zhu Li, Ph.D. (Young Investigator 2004) of Vanderbilt University, plans to study how atypical antipsychotic drugs contribute to acetylcholine (ACh) release and where in the brain these effects are mediated. Atypical antipsychotic drugs, such as clozapine and risperidone, but not typical antipsychotic drugs, such as haloperidol, preferentially increase ACh and dopamine (DA) release in the medial prefrontal cortex (mPFC) and hippocampus (HIP), effects believed to contribute to their ability to reverse cognitive dysfunction in schizophrenia. Dr. Li has evidence that an antagonist to the M1 muscarinic receptor increased ACh and DA release in the mPFC and HIP, and these increases were attenuated by telenzepine, an M1 antagonist, and by a 5-HT1A antagonist. Dr. Li proposes elucidating the role of M1 receptor activation in ACh release in the mPFC produced by atypical antipsychotic drugs in animal models. Understanding how atypical antipsychotic drugs increase ACh and DA release in rat mPFC and HIP would provide clues as to how to augment these effects in humans, possibly enhancing cognition.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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