Optimizing Working Memory: Effects Of Dopamine-Like Drug Enhances Short-Term Memory, Up To A Point

November 21, 1997

Short-term, or working, memory acts like a mental triage, of sorts. A small part of the brain in the prefrontal cortex is responsible for coordinating ephemeral sights, sounds, and smells before they're jettisoned or reserved for long-term keeping. Understanding the neurochemistry of how the brain's version of Post-It Notes works has long been the subject of intense research.

Recent studies have demonstrated a role for the neurotransmitter dopamine in orchestrating aspects of short-term memory. Now, a team of neuroscientists from the University of Pennsylvania Medical Center have demonstrated--for the first time--that a dopamine-like drug called bromocriptine can improve higher-level cognitive functions. What's more, the effects of bromocriptine depend on a person's baseline short-term memory capacity.

"Our a priori hypothesis was that the drug would improve performance in normal subjects," remarks Daniel Y. Kimberg, PhD, a post-doctoral fellow in the department of neurology, and lead author of the study. "After running a couple of pilot studies we noticed that subjects who did better on a reading memory test scored worse when performing the test a few hours after taking bromocriptine, and the ones who didn't do so well on the test seemed to improve on the drug."

When the subjects were divided into two groups based on their reading-memory-test scores, high-capacity subjects performed more poorly on four other tests that measure different aspects of working memory after taking bromocriptine; whereas, the scores of low-capacity subjects improved.

"The effect of baseline working memory capacity on the outcome of the experiment certainly surprised us," notes Mark D'Esposito, PhD, assistant professor of neurology and senior author of the study. "But we were equally surprised that such a low dose of any drug could alter cognitive function." The dose of bromocriptine--a common treatment for Parkinson's disease--given to subjects is the lowest available, so as to minimize the possibility of side effects.

The findings suggest that there is an optimal level of dopamine for short-term memory to function properly, and at high levels of working memory capacity and/or dopamine found naturally in the brain, more dopamine added to the system impairs rather than enhances performance.

The researchers did not set out to discover a way to improve short-term memory for everyday use. "Our aim was purely theoretical--to establish a link between dopamine and working memory in non-brain-injured humans," says D'Esposito. "Because of this finding, we repeated the study with frontal-brain-damaged subjects." The scores on the same memory tests conducted with these subjects improved after taking bromocriptine. It is these findings--presented earlier this year at the Academy of Neurology meeting--that may hold the most promise for clinical applications. In the near future, the researchers plan to repeat the study with other dopamine-like drugs. Using a functional MRI scanner, investigations are also underway to map where prefrontal activity occurs during the memory tests--both on and off the bromocriptine.

The team's study was reported in a November issue of NeuroReport. Penn scientist Martha J. Farah collaborated on this study, which was funded by the National Institutes of Health.

Editor's Note: Dr. D'Esposito can be reached at 215-349-8275 or despo@mail.med.upenn.edu, and Dr. Kimberg at 215-614-0177, or kimberg@mail.med.upenn.edu. For more information on D'Esposito's memory research consult: http://cortex.med.upenn.edu.

The University of Pennsylvania Medical Center's sponsored research ranks fifth in the United States, based on grant support from the National Institutes of Health, the primary funder of biomedical research in the nation. In federal fiscal year 1996, the medical center received $149 million. In addition, for the second consecutive year, the institution posted the highest growth rate in research activity--9.1 percent--of the top-ten U.S. academic medical centers during the same period. News releases from the medical center are available to reporters by direct E-mail, fax, or U.S. mail, upon request. They are also posted to the center's webpage (http://www.med.upenn.edu) and EurekAlert! (http://www.eurekalert.org), a resource sponsored by the American Association for the Advancement of Science.

University of Pennsylvania School of Medicine

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