Early Escalation of Cocaine Intake Is a Predictor of Addiction

New users of cocaine who quickly escalate the amount they are taking is a good predictor of who is likely to become addicted, a Yale study shows.

“While many people try drugs, only some actually become addicted,” said David Self, associate professor of psychiatry at Yale School of Medicine. “There are clear differences in individual vulnerability to develop addiction. We are interested in finding out what brain mechanisms account for the differences.”

His study, which was published in the May issue of the journal of Neuropsychopharmacology, was conducted on an animal model and tested three potential scenarios that might predict which animals would become addicted to cocaine. All of the animals were allowed to “self-administer” cocaine a few weeks earlier, then their access to the cocaine was removed and their craving for the drug was measured by the amount of lever-pressing they displayed in the drug’s absence.

The researchers tested the first hypotheses, which was that animals with higher activity in a new environment (novelty seekers) would self-administer cocaine to excessive levels. The second test was designed to determine if being sensitized to cocaine in low doses could predict addictive behavior.

“Neither a novelty response nor cocaine sensitization seemed to predict vulnerability to addiction,” said Self, principal investigator on the research project. “Although sensitization to drugs occurs in addiction, it does not seem to underlie drug craving.”

The third hypotheses was that animals with excessive craving responses would show differences in the amount of cocaine taken earlier in the testing. Indeed, the animals with the highest craving responses in abstinence showed a dramatic escalation of cocaine intake prior to abstinence. These animals totaled 35 percent of those being tested.

“A propensity for escalation and drug intake is, in itself, one of the criteria for addiction,” Self said. “We have identified the addictive population, but what we don’t know is how to screen these animals before they become addicted. We want to use this model to see if we can identify other behavioral features that predict which animals will show a vulnerability to develop cocaine addiction. We also want to know what is different about the brains of these animals.”

One possibility is that these animals show differences in dopamine signaling, a neurotransmitter that plays a key role in regulating both drug intake and craving. Self said the researchers also plan to identify differences in gene expression between the addicted and non-addicted animals using cDNA micro array profiling.

Other researchers on the project were Michael Sutton, a graduate student, and David Karanian, a research assistant in psychiatry.

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