YERKES RESEARCHERS FIRST TO DISCOVER COMBINATION OF DRUG THERAPIES REDUCES COCAINE USE

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YERKES RESEARCHERS FIRST TO DISCOVER COMBINATION OF DRUG THERAPIES REDUCES COCAINE USE
25 February 2007 - Emory University

Researchers at the Yerkes National Primate Research Center of Emory University are the first to demonstrate a combination of drug therapies targeting the region of the brain that controls drug abuse and addiction significantly reduces cocaine use in nonhuman primates. These findings, which appear in the June issue of the Journal of Pharmacology and Experimental Therapeutics, have implications for developing treatments for cocaine addiction in humans.

Led by Leonard Howell, PhD, an associate professor in Yerkes' Neuroscience Division, the Yerkes researchers observed the innovative combination of dopamine transporter inhibition and serotonin transporter inhibition was effective in limiting cocaine use in rhesus macaques who are trained to self-administer cocaine. "It appears DAT inhibition serves to substitute for cocaine, while SERT inhibition may limit the abuse potential of the medication," said Howell. "Our results, therefore, showing a combination of DAT and SERT inhibition were more effective than either alone are very promising."

This first-time finding was the promising end result of a several-step process. Howell and his colleagues began by administering a pretreatment of DAT inhibitors to confirm their effectiveness in reducing drug use. DAT inhibitors have long been used in addiction studies because they elicit reinforcing properties in the brain similar to those experienced as a result of taking cocaine.

The research team then substituted the DAT inhibitors for cocaine in order to determine their effectiveness in maintaining the use of the medications. Finally, Howell and the team administered a pretreatment with combined DAT inhibition and SERT inhibition, which is known to block the chemical effects of cocaine in the brain and reduce addictive properties, to determine if cocaine use was further reduced.

"Pretreatments with the combination therapy were very effective in eliminating cocaine use. Moreover, drug substitution tests with the medication indicated it should have limited abuse potential in humans," added Howell.

The research was supported by the U.S. Public Health Service and the National Institutes of Health.

Howell's next step is to determine an optimal dosing level for this combination strategy in order to develop the best potential treatment for cocaine addiction.

The Yerkes National Primate Research Center of Emory University is one of eight National Primate Research Centers funded by the National Institutes of Health. The Yerkes Research Center is a multidisciplinary research institute recognized as a leader in biomedical and behavioral studies with nonhuman primates. Yerkes scientists are on the forefront of developing vaccines for AIDS and malaria, and treatments for cocaine addiction and Parkinson's disease. Other research programs include cognitive development and decline, childhood visual defects, organ transplantation, the behavioral effects of hormone replacement therapy and social behaviors of primates. Leading researchers located worldwide seek to collaborate with Yerkes scientists.

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About: Emory University
Emory University is home to nine major academic divisions, numerous centres for advanced study, and a host of prestigious affiliated institutions. In addition to Emory College, the University encompasses a graduate school of arts and sciences; professional schools of medicine, theology, law, nursing, public health, and business; and Oxford College, a two-year undergraduate division on the original campus of Emory in Oxford, Ga.

Emory was founded at Oxford by the Methodist Church in 1836. Led by President James W. Wagner, an award-winning teacher and scholar, the University has 11,300 students and 2,500 faculty members who represent all regions of the United States and more than 100 foreign nations.

Emory University is known for its demanding academics, outstanding undergraduate college of arts and sciences, highly ranked professional schools and state-of-the-art research facilities. For more than a decade Emory has been named one of the country's top 25 national universities by U.S. News & World Report. In addition to its nine schools, the university encompasses The Carter Center, Yerkes National Primate Research Center and Emory Healthcare, a comprehensive metropolitan health care system.

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