Imaging Confirms Link between Receptor Levels and Cocaine Abuse

Using positron emission tomography (PET), researchers have established a firm connection between a particular brain chemistry trait and the tendency of an individual to abuse cocaine and possibly become addicted, suggesting potential treatment options.

The research, in animals, shows a significant correlation between the number of receptors in part of the brain for the neurotransmitter dopamine - measured before cocaine use begins - and the rate at which the animal will later self-administer the drug. The research was conducted in rhesus monkeys, which are considered an excellent model of human drug users.

Generally the lower the initial number of dopamine receptors, the higher the rate of cocaine use, the researchers found. The research was led by Michael A. Nader, Ph.D., professor of physiology and pharmacology at Wake Forest University School of Medicine.

It was already known that cocaine abusers had lower levels of a particular dopamine receptor known as D2, in both human and animal subjects, compared to non-users. But it was not known whether that was a pre-existing trait that predisposed individuals to cocaine abuse or was a result of cocaine use.

"The present findings in monkeys suggest that both factors are likely to be true," Nader and colleagues write in a study published online this week in the journal Nature Neuroscience. "The present findings also suggest that more vulnerable individuals are even more likely to continue using cocaine because of the cocaine-induced reductions in D2 receptor levels."

This was the first study ever to measure the baseline D2 levels of animals that had never used cocaine and compare those levels to changes in D2 receptors after the animals had started using. This kind of comparison is not possible with human subjects, and in previous monkey research, the brain chemistry of animals exposed to cocaine was compared only with non-using "controls."

The research also showed that starting to use cocaine caused the D2 levels to drop significantly and that continuing to use the drug kept the D2 levels well below the baseline.

"Overall, these findings provide unequivocal evidence for a role of [dopamine] D2 receptors in cocaine abuse and suggest that treatments aimed at increasing levels of D2 receptors may have promise for alleviating drug addition," the researchers write.

The study suggested that increasing D2 receptors might be done "pharmacologically" or by improving environmental factors, such as reducing stress. But, the study notes, "at present there are no clinically effective therapies for cocaine addiction, and an understanding of the biological and environmental mediators of vulnerability to cocaine abuse remains elusive."

Dopamine, like other neurotransmitters, moves between nerve cells in the brain to convey certain "messages." It is released by one nerve cell and taken in by the receptors on the next nerve cell, some of which are D2. Unused dopamine is collected in "transporters" that return it to the sending cell.