OHSU scientist helping explain basis of psychotic behavior

PORTLAND, Ore. -- An Oregon Health & Science University researcher is among an international team closing in on why many people with schizophrenia and other psychotic disorders are "supersensitive" to the powerful neurotransmitter dopamine.

David Grandy, Ph.D., associate professor of physiology and pharmacology, OHSU School of Medicine, co-authored a study appearing recently in Proceedings of the National Academy of Sciences that found a link between dopamine supersensitivity and increased levels of a dopamine receptor with a particularly high affinity for dopamine.

Dopamine is a neurotransmitter found in the brain that plays an important role in the regulation of behavior involved in movement control, motivation and reward, and the dopamine system is thought to be essential to the brain's response to drugs of abuse, especially opiates and psychostimulants.

Supersensitivity to dopamine, which affects some 70 percent of individuals with schizophrenia, can take the form of a low tolerance to antipsychotics, amphetamines and other drugs, including drugs of abuse, that trigger dopamine's release in the brain. The latest discovery could someday lead to the development of drug therapies that temporarily bring people with psychosis into a more normal, less-sensitive state and make them more amenable to antipsychotic treatment.

It also could help scientists find ways to turn down the activity of the dopamine D2 receptor in individuals for whom dopamine sensitivity can be dangerous, such as prolonged drug abusers.

"It does appear that wherever you see supersensitivity, you see high-affinity dopamine D2 receptors as the predominant form," said Grandy, a pioneer in the study of the dopamine neurotransmitter system. "But to say you're going to then reverse supersensitivity by changing the D2-high status, we haven't done that. To do that, we have to be able to selectively manipulate the system in such a way that we could drive the receptor

Contact: Jonathan Modie
503 494-8231
Oregon Health & Science University

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