How Psychostimulants Disrupt The Brain’s Normal Functioning

How cocaine and amphetamines disrupt the normal functioning of the dopamine transporter in the brain has been illuminated, in a major advance in the field of neuropsychiatry, by researchers in the Vollum Institute at Oregon Health & Science University.

The discovery opens the door to 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.

Blocked Neurotransmitter Pump

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.

Eric Gouaux, Ph.D., senior scientist in the Vollum Institute at OHSU, said:

“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.”

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.

Richard Goodman, M.D., Ph.D., director of the Vollum Institute at OHSU, said:

“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. In light of the profound economic and social costs of drug addiction in the U.S., this research could have a transformative effect.”

The paper is the fruit 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.

Reference:

Kevin H. Wang, Aravind Penmatsa & Eric Gouaux
Neurotransmitter and psychostimulant recognition by the dopamine transporter
Nature (2015) doi:10.1038/nature14431

Image: Surian Soosay/Flickr