Featured Research

from universities, journals, and other organizations

OHSU Scientist Helping Explain Basis Of Psychotic Behavior

Date:
May 14, 2005
Source:
Oregon Health & Science University
Summary:
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 neurotransmitter dopamine. Dr. David Grandy co-authored a study that found a link between dopamine supersensitivity and increased levels of a dopamine receptor with a particularly high affinity for dopamine. The discovery could lead to the development of drug therapies that make people more amenable to antipsychotic treatment.

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.

Related Articles


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 from high-to low-affinity or otherwise effect its ability to signal efficiently by some drug treatment."

While supersensitivity is only determined by observing behavioral changes, and the high-affinity D2 is verified pharmacologically, "what we're showing is a very strong correlation between the presence of a higher proportion of high-affinity D2 in a population of receptors in animals that show supersensitivity to dopaminergic drugs," Grandy added.

The study also further confirms the importance of the dopamine system in understanding and treating psychosis.

"The bottom-line, take-home message is that there are a lot of different things that all seem to converge on this system," Grandy said. "It's like all roads lead to Rome. The D2 system still seems to be very important in terms of psychosis and amphetamine-mediated disorders."

To create dopamine supersensitivity in animal models, researchers used mice bred to lack the D2 gene as well as rats treated with PCP, alcohol, amphetamine and other dopamine-inducing drugs. They found that while there were small increases in the total population of D2 receptors among the animal models, the increases were small compared with the jump in densities of D2 receptors in the high-affinity state.

The protein product of the dopamine D2 receptor gene already is the primary target for antipsychotic drugs used to treat schizophrenia, prolonged drug abuse and other diseases with psychotic symptoms. But scientists are only beginning to understand the cascade of events that allow dopamine receptors to signal that they have found and bound the neurotransmitter dopamine.

"The more we understand about the receptors, their physical characteristics, how they put themselves into this high-affinity state, and then signal this event in the brain, the closer we'll be to better treating and maybe even preventing the development of psychoses," Grandy said.

###

The study was led by Philip Seeman, M.D., Ph.D., professor emeritus of pharmacology at the University of Toronto, Canada. Grandy's work in this study was supported by the National Institute on Drug Abuse and the National Institute of Mental Health.

To access all OHSU news releases, visit www.ohsu.edu/news/

Technology used in this research is covered under non-exclusive license agreements through which OHSU and Dr. Grandy have the potential to derive future income. This potential conflict was reviewed and a management plan approved by the OHSU Conflict of Interest in Research Committee was implemented.


Story Source:

The above story is based on materials provided by Oregon Health & Science University. Note: Materials may be edited for content and length.


Cite This Page:

Oregon Health & Science University. "OHSU Scientist Helping Explain Basis Of Psychotic Behavior." ScienceDaily. ScienceDaily, 14 May 2005. <www.sciencedaily.com/releases/2005/05/050513225928.htm>.
Oregon Health & Science University. (2005, May 14). OHSU Scientist Helping Explain Basis Of Psychotic Behavior. ScienceDaily. Retrieved November 26, 2014 from www.sciencedaily.com/releases/2005/05/050513225928.htm
Oregon Health & Science University. "OHSU Scientist Helping Explain Basis Of Psychotic Behavior." ScienceDaily. www.sciencedaily.com/releases/2005/05/050513225928.htm (accessed November 26, 2014).

Share This


More From ScienceDaily



More Mind & Brain News

Wednesday, November 26, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Are Female Bosses More Likely To Be Depressed?

Are Female Bosses More Likely To Be Depressed?

Newsy (Nov. 24, 2014) A new study links greater authority with increased depressive symptoms among women in the workplace. Video provided by Newsy
Powered by NewsLook.com
Winter Can Cause Depression — Here's How To Combat It

Winter Can Cause Depression — Here's How To Combat It

Newsy (Nov. 23, 2014) Millions of American suffer from seasonal depression every year. It can lead to adverse health effects, but there are ways to ease symptoms. Video provided by Newsy
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Milestone Birthdays Can Bring Existential Crisis, Study Says

Milestone Birthdays Can Bring Existential Crisis, Study Says

Newsy (Nov. 21, 2014) Researchers find that as people approach new decades in their lives they make bigger life decisions. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins