Featured Research

from universities, journals, and other organizations

New Mechanism Found For Neurodegenerative Effects Of Amphetamines In Mice

Date:
April 5, 2006
Source:
University of Toronto
Summary:
Researchers have discovered a new mechanism for the neurodegenerative effects of amphetamines. These drugs are converted in the brain into free radicals, highly reactive molecules that cause neurodegenerative brain damage and whose effects manifest and linger long after the amphetamine has left the body.

University of Toronto researchers have discovered a new mechanism for the neurodegenerative effects of amphetamines. These drugs are converted in the brain into free radicals, highly reactive molecules that cause neurodegenerative brain damage and whose effects manifest and linger long after the amphetamine has left the body.

"The question of whether amphetamines like ecstasy (MDMA) or methamphetamine (METH) cause neurodegeneration in humans is one of the most controversial areas in science today," says Professor Peter Wells of the Leslie Dan Faculty of Pharmacy, lead author of the study that appears in the April issue of the Journal of the Federation of American Societies for Experimental Biology (FASEB Journal). "The short-term effects of these drugs -- hypothermia, electrolyte imbalances and an elevated risk of heart attack -- are well understood, but not their long-term consequences."

Wells and doctoral students Winnie Jeng, Annmarie Ramkissoon and Toufan Parman theorized that prostaglandin H synthase (PHS) -- an enzyme that synthesizes a range of hormones throughout mammalian life -- is the catalyst that transforms amphetamines into free radical products that react with oxygen in the body to enhance the formation of highly toxic reactive oxygen species. These toxic forms of oxygen are implicated in neurodegenerative diseases such as Alzheimer's and Parkinson's because of the increased oxidative stress they place on the body, resulting in irreversible damage to DNA, proteins and lipid membranes. Organs such as the brain, which lack abundant antioxidant protection, are particularly vulnerable to oxidative stress.

To approximate an acute human exposure, the researchers administered four doses of either MDA (the major metabolite of ecstasy) or METH at two-hour intervals to young adult mice. In the case of MDA, before the first drug injection an additional group of mice was given a single dose of aspirin (acetylsalicylic acid), which is known to inhibit PHS and block its ability to convert drugs to free radical products. Over a six-month period, following the single day's treatment of MDA or METH, the mice were observed and had their motor co-ordination tested by walking on a rotating rod. Normally, mice balance easily on the rods for extended periods. Within two weeks of the last treatment, all the mice given MDA or METH without aspirin had trouble with this task and remained disabled for at least six months. These mice also exhibited enhanced molecular damage to the DNA in their brains and a loss of nerve terminals that remained for at least one week after exposure to MDA or METH. The mice pretreated with aspirin had less molecular damage to their DNA and fewer motor disabilities, suggesting that the neurodegenerative effects of MDA are dependent upon its conversion by PHS into a reactive free radical product.

"Our findings reveal how exquisitely susceptible brains are to this kind of damage, at least in mice," Wells says. "The long-term negative effects in the mice treated with MDA or METH all resulted from a single day's dosage that approximated the higher range of human exposures."

Although the team's findings cannot be extrapolated to humans without further study, Wells believes they do suggest a novel mechanism through which amphetamines may contribute to neurodegeneration.

"Our hypothesis about PHS-catalyzed conversation may also be relevant to the neurodegenerative risks associated with aging," he says. "Preliminary results from other studies suggest that PHS may convert other compounds in our brains into free radicals, and there is some evidence in the clinical literature that suggests patients who take high doses of PHS-inhibiting drugs such as aspirin may experience less neurodegeneration. The potential of substances like aspirin to prevent neurodegenerative damage merits more examination, particularly among people who take it chronically for pain."

This study was funded by the Canadian Institutes of Health Research, with support from the National Institute on Drug Abuse (U.S.A) and Health Canada's Healthy Environments and Consumer Safety Branch.


Story Source:

The above story is based on materials provided by University of Toronto. Note: Materials may be edited for content and length.


Cite This Page:

University of Toronto. "New Mechanism Found For Neurodegenerative Effects Of Amphetamines In Mice." ScienceDaily. ScienceDaily, 5 April 2006. <www.sciencedaily.com/releases/2006/04/060405233546.htm>.
University of Toronto. (2006, April 5). New Mechanism Found For Neurodegenerative Effects Of Amphetamines In Mice. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2006/04/060405233546.htm
University of Toronto. "New Mechanism Found For Neurodegenerative Effects Of Amphetamines In Mice." ScienceDaily. www.sciencedaily.com/releases/2006/04/060405233546.htm (accessed July 29, 2014).

Share This




More Mind & Brain News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Losing Sleep Leaves You Vulnerable To 'False Memories'

Losing Sleep Leaves You Vulnerable To 'False Memories'

Newsy (July 27, 2014) A new study shows sleep deprivation can make it harder for people to remember specific details of an event. Video provided by Newsy
Powered by NewsLook.com
University Quiz Implies Atheists Are Smarter Than Christians

University Quiz Implies Atheists Are Smarter Than Christians

Newsy (July 25, 2014) An online quiz from a required course at Ohio State is making waves for suggesting atheists are inherently smarter than Christians. Video provided by Newsy
Powered by NewsLook.com
Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

AFP (July 24, 2014) A so-called drugs rehab 'clinic' is closed down in Pakistan after police find scores of ‘patients’ chained up alleging serial abuse. Duration 03:05 Video provided by AFP
Powered by NewsLook.com
New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. 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:
from the past week

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