Researchers discover how cocaine, amphetamines disrupt the brain’s normal functioning

05/11/15  Portland, Ore.

Research sheds light on how addictive drugs interfere with the dopamine transporter, expected to usher in long-sought advances in treatments

In a major advance in the field of neuropsychiatry, researchers in the Vollum Institute at Oregon Health & Science University have illuminated how cocaine and amphetamines disrupt the normal functioning of the dopamine transporter in the brain. This discovery paves the way for developing treatments that could blunt the effects of cocaine and amphetamines in patients who are addicted.

Currently, there are no approved drug therapies for amphetamine abuse, and the rate of relapse for people addicted to cocaine and amphetamines is high. The researchers’ work was published online today in the journal Nature.

The dopamine transporter serves as a 'pump' that removes the neurotransmitter from the synapse, or the regions of nerve cell to nerve cell communication. Amphetamines and cocaine block dopamine signaling by interfering with the dopamine transporter.

“Addiction to amphetamines and cocaine devastates lives, families and communities in Oregon and across the U.S. Our research pinpoints how these addictive drugs interfere with the dopamine transporter and normal signaling in the brain, bringing us closer to developing effective treatments for people who are addicted to cocaine and amphetamines,” said Eric Gouaux, Ph.D., senior scientist in the Vollum Institute at OHSU, and Howard Hughes Medical Institute Investigator.

In showing how cocaine and amphetamine block normal dopamine signaling, the research provides insights, which may, in turn, lead to an understanding of why some drugs are addictive and others are not. It also opens the door to the development of drugs that could block the interference of cocaine and amphetamine with dopamine signaling.

“This research paper fills in a major gap in our knowledge that’s persisted for decades: how exactly these highly addictive drugs impact normal brain functioning. This groundbreaking research arms the pharmaceutical industry with specific information about targets for treatment, opening the door for new therapeutic approaches for blocking the effects of cocaine and amphetamine.” said Richard Goodman, M.D., Ph.D., director of the Vollum Institute at OHSU. “In light of the profound economic and social costs of drug addiction in the U.S., this research could have a transformative effect."

This paper is the culmination of more than 20 years of work at the Vollum Institute investigating regulation of the critically important dopamine transporter, a protein that has key contributions to such neuropsychiatric diseases as schizophrenia, depression, drug abuse behavior, and attention deficit disorder. The economic cost of mental illness in the U.S. is now estimated to be more than $300 billion annually, with 20 percent of adults reporting a diagnosable mental illness each year.

“Neurotransmitter and psychostimulant recognition by the dopamine transporter” was authored by Gouaux; Kevin Wang, Ph.D., Vollum Institute at OHSU; Aravind Penmatsa, Ph.D., Vollum Institute at OHSU.

This work was supported by a National Institutes of Mental Health Ruth Kirschstein postdoctoral fellowship (F32 MH093120) and Brain and Behavior Research Foundation Young Investigator research award (22655), a postdoctoral fellowship from the American Heart Association (11POST7370096), and by the National Institutes of Health and the Methamphetamine Abuse Research Center of OHSU (P50DA018165).

About OHSU

Oregon Health & Science University is a nationally prominent research university and Oregon’s only public academic health center. It serves patients throughout the region with a Level 1 trauma center and nationally recognized Doernbecher Children’s Hospital. OHSU operates dental, medical, nursing and pharmacy schools that rank high both in research funding and in meeting the university’s social mission. OHSU’s Knight Cancer Institute helped pioneer personalized medicine through a discovery that identified how to shut down cells that enable cancer to grow without harming healthy ones. OHSU Brain Institute scientists are nationally recognized for discoveries that have led to a better understanding of Alzheimer’s disease and new treatments for Parkinson’s disease, multiple sclerosis and stroke. OHSU’s Casey Eye Institute is a global leader in ophthalmic imaging, and in clinical trials related to eye disease.