05:21am Monday 18 December 2017

Cocaine is Direct Cause of Cognitive Deficits, Says University of Pittsburgh Team

A wide range of cognitive difficulties are seen among cocaine users, but it hasn’t been clear whether that reflects pre-existing traits that made them more susceptible to drug abuse or to the drug itself, said senior investigator Charles W. Bradberry, Ph.D., associate professor of psychiatry at Pitt School of Medicine.

“It’s well known that the level of cognitive deficit can predict how successful treatment is likely to be,” he said. “If we understand what the problems are and whether the drug itself was the cause, then we might be able to design treatments that have a better chance of working.”

For the study, the researchers assessed cognitive skills in 14 rhesus monkeys that learned to touch an abstract shape on a touch screen to receive either a sip of water or a cocaine infusion via a special access port into a blood vessel. Within a week, the cocaine group was regularly self-administering the maximum of six doses daily from Tuesdays to Fridays.

On Mondays, after three days without receiving drugs, the monkeys’ associative learning skills were assessed. Each animal was presented with two consistent stimuli on the touch screen with a correct answer recorded for touching the one associated with a higher volume of water reward. But once a threshold number of correct answers was achieved, the rules were reversed, with the high stimulus becoming low and the low becoming high.

The researchers found that the cocaine group learned the initial rules as quickly and at first responded as accurately as the water-only group, but only five of the eight achieved the threshold of correct responses. The researchers then increased the difference between high and low rewards, which allowed the remaining three monkeys in the cocaine group to get to threshold.

“That tells us the cocaine users have a hard time maintaining focus and attention,” Dr. Bradberry said. “But if we increase the reward value of these things they’re trying to learn, we can overcome that cognitive deficit.”

He added that once the stimuli were reversed, the cocaine group had much greater difficulty learning and adapting to the change in rules, indicating a deficit in cognitive control processes or executive brain functions that require focus and  guide volitional, goal-directed behavior.

In another task, the animals saw a single image that when touched resulted in a supplemental water reward. Then they were shown the same image along with a random one, and if they chose the correct one after a delay of up to 40 seconds they got the reward. The cocaine group’s performance was less accurate as the delay increased.

“This experiment reveals that cocaine use causes impairments of visual working memory,” Dr. Bradberry said. “Like the inability to maintain consistent levels of accuracy in the other task, this could reflect problems with attention in addition to the impairment in cognitive control.”

His team now is using imaging tools to see how the brain’s structure might change due to cocaine exposure.

Co-authors of the paper include Jessica N. Porter, Ph.D. candidate, Adam S. Olsen, Kate Gurnsey, Brian P. Dugan, and Hank P. Jedema, Ph.D., all of the University of Pittsburgh.

The study was funded by the National Institute on Drug Abuse, part of the National Institutes of Health; and the Veterans Affairs Medical Research Service.

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About the University of Pittsburgh School of Medicine

As one of the nation’s leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1997 and now ranks fifth in the nation, according to NIH data for 2008 (the most recent year for which the data are final).

Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region’s economy. For more information about the School of Medicine, see www.medschool.pitt.edu.


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