Repeated Cocaine Use Impairs Region of the Brain That Governs Self Control

Taking cocaine impairs the orbitofrontal cortex, an area of the brain responsible for self control and decision making, and the effects persist long after the cocaine use stops, a behavioral study by a Yale researcher and collaborator has found.

Taking cocaine impairs the orbitofrontal cortex, an area of the brain responsible for self control and decision making, and the effects persist long after the cocaine use stops, a behavioral study by a Yale researcher and collaborator has found.

“It’s thought that this impairment in inhibitory control may contribute to certain aspects of drug abuse, such as craving, binging, and risky behaviors,” said Jane Taylor, associate professor in the division of molecular psychiatry at Yale School of Medicine and senior author of the study published in the February issue of Neuropsychopharmacology.

In addition to impairing orbitofrontal cortex function, the researchers observed in their study of primates exposed to cocaine that the primates’ behavior indicated disruption in this area up to one month later.

The study funded by the National Institute on Drug Abuse was designed to help answer the question of whether drug abusers are born with an impairment in the frontal cortex, or whether the problem develops as a consequence of drug use.

Taylor and the lead author of the study, David Jentsch, now at UCLA, observed how prior cocaine exposure affects the primates’ reversal learning ability, which is an activity that takes place in the orbitofrontal cortex. This same area of the brain, located in the ventromedial region of the frontal cortex, has been implicated in recent imaging studies of drug abusers.

The primates were first trained to discriminate that food was available only under one of three novel objects. Then the food was placed under one of the other objects. The primates then had to inhibit their response to the former object and choose the other object. Those injected with saline were able to change their behavior. Those injected with cocaine were not able to inhibit their earlier response and continued to reach toward the original object.

“While these deficits could be interpreted as indicating that addicts have an underlying orbitofrontal dysfunction that predisposes them to drug abuse, our results indicate that prior cocaine exposure is sufficient to produce cognitive deficits reminiscent of orbitofrontal cortical dysfunction,” the researchers said in the study. “Therefore, the frontal lobe impairments in drug abusers may be a consequence of, as well as a pre-disposing factor to, addiction.”

Taylor said it is difficult to conduct similar tests with drug addicts because it is almost impossible to separate out a drug problem from other possible psychiatric disorders, or to control for the fact that the addicts are often taking other drugs as well.

Another paper in the February issue of Biological Psychiatry showing decreased gray matter in the orbital frontal cortex of cocaine abusers is consistent with recent clinical data and the current Yale study that together demonstrate long lasting cocaine induced deficits in inhibitory control and decision making.

The Yale study was conducted at the St. Kitts Biomedical Primate Research facility, and the other contributing researchers were Peter Olausson at Yale and Richard De La Garza II, now at Albert Einstein College of Medicine.

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