Yale Bulletin and Calendar

November 1-8, 1999

Volume 28, Number 11

Study shows long-lasting effects of
low-dose amphetamine use has long-lasting

Repeated exposure to low-dose amphetamines can impair how the brain functions, and the effects can last for several years after the exposure ends, a Yale study has found.

The research offers insights into the potential harmful effects of chronic substance abuse in humans.

While previous studies have shown that high levels of amphetamine injections are harmful to the brain, "our report is the first to demonstrate long-lasting ... and possibly permanent cognitive deficits induced by a brief period of intermittent low-dose amphetamine exposure," says Stacy Castner, a researcher on the study. "This research could also lead to potential treatment of cognitive impairment in former drug abusers as well as potential drug deterrents in adolescents and young adults."

To mimic the "binge/crash" pattern of drug abuse in humans, Castner gave primates twice-daily injections of chronic amphetamine (AMPH), five days per week for six weeks. The AMPH dose ranged from 0.1 mg/kg to 1.0 mg/kg and was increased by 0.1 mg/kg every three drug days.

The investigators assessed changes in behavior and videotaped the primates to record behavioral responses to each dose of AMPH. At six months into the amphetamine exposure, the primates were tested on an array of cognitive tasks ranging from recognition memory, visual discrimination and spatial working memory. Primates previously exposed to amphetamines failed to perform the tasks successfully even with continued testing, for up to one and a half years.

"The results show the presence of profound cognitive deficits in the amphetamine-treated animals," says Castner, associate research scientist in neurobiology. "This finding could also lead to further understanding of other diseases involving dysregulation of the brain's dopamine neurons."

The study, which was highlighted at the Society for Neuroscience annual meeting in Miami, Florida Oct. 23-28, is consistent with data from human research where commonly abused drugs such as cocaine and Ecstasy have been found to produce long-lasting and possibly permanent harmful effects on the brain.

"It may be the case that even a brief period of low-dose amphetamine abuse in early adolescence or early adulthood can produce profound cognitive deficits that may persist for a couple of years or more after amphetamine use has ended," says Castner.

The investigators' ongoing research includes experiments involving neurotransmitters that will help explain the long-lasting cognitive impairment in primates. They are also conducting experiments to reverse the AMPH-induced cognitive problems in the same group of primates, and they plan to investigate the biochemical and structural changes in the primate brain that could account for the behavioral deficits.

This study was supported by the Center for Neuroscience in Mental Disorders from the National Institutes of Health. Patricia S. Goldman-Rakic, professor of neurobiology at Yale, was principal investigator.

-- By Karen Peart

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