Researchers at the Yerkes National Primate Research Center are
the first to demonstrate that a combination of drug therapies targeting
the region of the brain that controls drug abuse and addiction
significantly reduces cocaine use in nonhuman primates.
The 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, an associate professor in Yerkes’ neuroscience division,
the researchers observed the innovative combination of dopamine transporter (DAT)
inhibition and serotonin transporter (SERT) inhibition was effective in limiting
cocaine use in rhesus macaques 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,” Howell said. “Our
results, showing a combination of DAT and SERT inhibition were more effective
than either alone, are very promising.”
This first-time finding was the 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 long have been
used in addiction studies because they elicit reinforcing properties in the brain
similar to those experienced from cocaine 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 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
“Pretreatments with the combination therapy were very effective in eliminating
cocaine use,” Howell said. “Moreover, drug substitution tests
with the medication indicated it should limit abuse potential in humans.”
The research was supported by the U.S. Public Health Service and the National
Institutes of Health.
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 in reducing cocaine self-administration.
The next step, he said, is to determine an optimal dosing level for this combination
strategy in order to develop the best potential treatment for cocaine addiction.