By studying the dopamine system in cocaine-addicted rats.
According to the Substance Abuse and Mental Health Services Administration, over 700,000 people in the United States alone are affected by cocaine addiction. There’s currently no effective treatment available for cocaine addiction, so it’s critical that research brings us to a better understanding of the underlying brain mechanisms to target.
Now, researchers at Wake Forest Baptist have brought us one step closer to understanding why cocaine is so addictive through their work with rats, which has been published in the Journal of Neuroscience.
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"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," lead author Sara R. Jones, professor of physiology and pharmacology at Wake Forest Baptist, said in a media statement.
In an experiment with rats, the scientists replicated cocaine addiction by enabling the rats to self-administer as much cocaine as they desired (up to 40 doses) during a six-hour period. They repeated this for five days.
According to Jones, six hours of cocaine access a day is enough to send the animals over the edge from having a controlled intake to a more uncontrolled, binge-like behavior.
After the five days were up, the cocaine-addicted rats weren’t allowed to indulge in cocaine for either 14 or 60 days, depending on where they were grouped. The researchers studied the rats’ dopamine transporters, and surprisingly, they appeared normal — they looked just like those in the control animals who had received saline instead of cocaine.
However, what the researchers observed after the rats finally got a dose of cocaine after the period of abstinence is where things get interesting.
Even after 60 days, a single self-administered infusion of cocaine completely reinstated the rats’ tolerance to cocaine’s effects. This effect wasn’t seen in the control animals who had never received cocaine.
According to Jones, this data suggests there is a “priming effect,” meaning that cocaine leaves a long-lasting imprint on the dopamine system and becomes activated by re-exposure to the drug.
Cocaine addiction is characterized by the high tolerance that develops after repeated use, as well as repeated attempts at abstinence that often results in relapse. The researchers say that this “priming effect” may be permanent, so it could contribute to the severity of relapse episodes seen 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."
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