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Yerkes Researchers First to Discover Combination of Drug Therapies Reduces Cocaine Use in Nonhuman Primates

May 24, 2004

Findings Have Implications for Developing Treatments for Cocaine Addiction

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Lisa Newbern, 404-727-7709,

ATLANTA — 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 controlling 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, may have implications for developing treatments for cocaine addiction.

Researchers led by Leonard Howell, PhD., an associate professor in the Neuroscience Division at the Yerkes Research Center, first administered a pretreatment of dopamine transporter (DAT) inhibitors, substances long-used in addiction studies because they elicit reinforcing properties in the brain similar to those experienced as a result of taking cocaine, to rhesus macaques trained to self-administer cocaine, to confirm their effectiveness in reducing drug use. 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’s team combined the DAT inhibitors with serotonin transporter (SERT) inhibitors, known to block the chemical effects of cocaine in the brain and so reduce the addictive properties, to determine if cocaine use was further reduced. The researchers observed the innovative combination of DAT and SERT inhibitors was most effective in limiting cocaine use in the rhesus macaques.

“DAT inhibitors are effective substitutes for cocaine because they share similar pharmacological properties, however there could be potential to abuse the DAT inhibitors themselves for the same reasons,” said Howell. “On the other hand, while SERT inhibitors effectively block the actions of cocaine on the brain, they do not share any cocaine-like properties so there is little incentive to continue their use, and compliance becomes an issue.”

On June 16 at the annual meeting of the College of Problems of Drug Dependence in San Juan Puerto Rico, Howell will present a subsequent study in which his team determined fluoxetine (Prozac), a SERT inhibitor, enhanced the effectiveness of a DAT inhibitor to reduce cocaine self-administration.

“Our goal for these studies was to find potential drug therapies to treat cocaine abuse,” said Howell. “It appears DAT inhibition serves to substitute for cocaine, while SERT inhibition may limit the abuse potential of the medication. Therefore, our results, showing a combination of DAT and SERT inhibition were more effective than either alone, are very promising.”

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

The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service. Its components include the Emory University School of Medicine, Nell Hodgson Woodruff School of Nursing, and Rollins School of Public Health; Yerkes National Primate Research Center; Winship Cancer Institute of Emory University; and Emory Healthcare, the largest, most comprehensive health system in Georgia. Emory Healthcare includes: The Emory Clinic, Emory-Children's Center, Emory University Hospital, Emory University Hospital Midtown, Wesley Woods Center, and Emory University Orthopaedics & Spine Hospital. The Woodruff Health Sciences Center has a $2.5 billion budget, 17,600 employees, 2,500 full-time and 1,500 affiliated faculty, 4,700 students and trainees, and a $5.7 billion economic impact on metro Atlanta.

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