Scientists at Wake Forest Baptist Medical
Center are one step closer to understanding what causes cocaine to be so
addictive. The research findings are published in the current issue of the
Journal of Neuroscience.
Cocaine addiction is a debilitating neurological disorder
that affects more than 700,000 people in the United States alone, according to
the Substance Abuse and Mental Health Services Administration. With repeated
use, tolerance may develop, meaning more of the drug is required to achieve the
same euphoric effect. Cocaine addiction is characterized by repeated attempts
at abstinence that often end in relapse.
“Scientists have known for years that cocaine affects the
dopamine system and dopamine transporters, so we designed our study to gain a
better understanding of how tolerance to cocaine develops via the dopamine
transporters,” said Sara R. Jones, Ph.D., professor of physiology and
pharmacology at Wake Forest Baptist and lead author of the study.
“Currently there isn’t any effective treatment available
for cocaine addiction so understanding the underlying mechanism is essential
for targeting potential new treatments.”
Using an animal model, the research team replicated
cocaine addiction by allowing rats to self-administer as much cocaine as they
wanted (up to 40 doses) during a six-hour period. Six-hour-a-day access is long
enough to cause escalation of intake and tip animals over from having
controlled intake to more uncontrolled, binge-like behavior, Jones said.
Following the five-day experiment, the animals were not
allowed cocaine for 14 or 60 days. After the periods of abstinence, the
researchers looked at the animals’ dopamine transporters and they appeared normal,
just like those in the control animals that had only received saline.
However, a single self-administered infusion of cocaine
at the end of abstinence, even after 60 days, fully reinstated tolerance to
cocaine’s effects in the animals that had binged. In the control animals that
had never received cocaine, a single dose did not have the same effect.
These data demonstrate that cocaine leaves a long-lasting
imprint on the dopamine system that is activated by re-exposure to cocaine,
Jones said. This ‘priming effect,’ which may be permanent, may contribute to
the severity of relapse episodes in cocaine addicts.
“Even after 60 days of abstinence, which is roughly
equivalent to four years in humans, it only took a single dose of cocaine to
put the rats back to square one with regard to its’ dopamine system and
tolerance levels, and increased the likelihood of binging again,” Jones said. “It’s
that terrible cycle of addiction.”
Jones added that hope is on the horizon through
preclinical trials that are testing several drugs for
effectiveness in treating cocaine addiction.
The research was supported by National Institutes of
Health grants RO1 DAO21325, RO1DAO30161, F31DAO37710 and T32AA00757565.
Co-authors are Cody A. Siciliano, Ph.D., and Steve C. Fordahl, Ph.D., of Wake Forest