Pubdate: Tue, 04 Mar 2003
Source: Enid News & Eagle (OK)
Copyright: Enid News & Eagle 2003
Contact:  http://www.enidnews.com/
Details: http://www.mapinc.org/media/2012
Author: Jill S. Williams, NIDA NOTES Contributing Writer

PRENATAL EXPOSURE TO ECSTASY MAY IMPAIR MEMORY AND COGNITION

Dr. Harry Broening, Dr. Charles Vorhees, and colleagues at the Cincinnati 
Children's Research Foundation and the University of Cincinnati have 
demonstrated that rats exposed to MDMA -- ecstasy -- during the 
developmental period corresponding to the third trimester of human 
pregnancy suffer memory and learning deficiencies that persist into adulthood.

Scientific studies have already established that ecstasy users are at risk 
for dehydration, hypertension, hyperthermia, and heart or kidney failure. 
The drug also has been shown to damage nerves in the brain's serotonin 
system and appears to produce long-term deficits in memory and cognition.

The new study suggests that unborn children of ecstasy users may suffer 
deleterious effects that last into adulthood. "The possibility that these 
findings in rats may also apply to humans raises a concern because this 
drug, which is incorrectly perceived as safe by many of its proponents, is 
sometimes being used by young women who are pregnant," says Dr. Jerry 
Frankenheim of NIDA's Division of Neuroscience and Behavioral Research.

Animals Exposed to MDMA Take Longer To Escape Multiple-T Water Maze

Adult rats that had been exposed to MDMA doses of 10 or 20 mg/kg body 
weight (comparable to doses used by human MDMA abusers) on days 11 to 20 
after birth (a period comparable to late in the third trimester of human 
pregnancy) took significantly longer to escape the multiple-T water maze 
than did animals exposed to saline solution. No statistically significant 
increase in escape times was observed among rats exposed on days 1 to 10 
after birth.

Timing and Vulnerability

In designing the current study, the researchers drew on previous studies by 
Dr. Vorhees on the effects of methamphetamine exposure on rodent brain 
development. These studies identified specific periods late in rodent brain 
development -- days 11 to 20 after birth, which are analogous to late 
third-trimester human fetal brain development -- in which the brain is 
quite vulnerable to methamphetamine-induced impairments of spatial learning 
and memory.

The question became, can related drugs, such as MDMA and other synthetic 
stimulants, also cause such impairments? Dr. Vorhees and his colleagues 
decided to test the effects of MDMA administered to rats at this same 
crucial 11 to 20 days postnatal developmental period and to a comparison 
group of rats on days 1 to 10 after birth (comparable to early third 
trimester of human pregnancy).

According to Dr. Vorhees, the dosages given to rats in the study are 
equivalent to a 110-lb woman taking 25 mg, a common dose for MDMA users, up 
to 250 mg, an amount sometimes reached or exceeded by chronic abusers. 
Testing for Learning, Memory When the rats reached young adulthood, the 
researchers put them through a series of maze and swimming trials to assess 
the effects of MDMA exposure on learning and memory. An initial test 
revealed no significant differences between the MDMA-exposed rats and the 
controls in terms of swimming performance or motivation to escape from the 
water.

Next, animals were evaluated in a test of sequential learning called the 
multiple-T (Cincinnati) water maze. The rats had to search through nine 
decision points to find their way through the maze and out of the water. 
The researchers found that the rats exposed to MDMA on days 11 to 20 after 
birth made significantly more errors and took significantly longer to 
escape the maze than did either the MDMA-unexposed animals or those exposed 
to MDMA on days 1 to 10 after birth.

"The animals exposed to MDMA during the critical 11 to 20 days postnatal 
brain development period cannot seem to eliminate errors the way normal 
animals do," says Dr. Vorhees. "The difference is the rate at which they 
learn. All of the animals eventually learned how to navigate the maze, but 
it took the MDMA-exposed animals significantly longer to do so."

The Morris hidden platform maze was used to further evaluate the animals' 
spatial memory and cognitive abilities. A 6-foot diameter swimming pool was 
constructed and a small clear acrylic platform was placed so that the 
animals could escape if they found it. In increasingly difficult phases the 
rats had to find the platform when it was above the water, below the water, 
moved to a new location, or below the water and reduced in size. Memory 
trials were also performed with the platform removed.

Animals exposed to MDMA on days 1 to 10 after birth performed as well as 
unexposed animals on the trials. However, the animals exposed to MDMA on 
days 11 to 20 after birth showed significant impairment of memory and 
spatial learning when the platform was submerged and on memory trials when 
the platform was removed, but no differences when the platform was above 
the water.

"These later trials test the animals' ability to remember something in 
space," explains Dr. Vorhees. "We found that as we made the task harder, 
MDMA-exposed animals had a disproportionately harder time finding the 
platform. The harder the task was, the more their learning disability was 
revealed." Comparing Infant Versus Adult Exposure Upon completion of the 
trials, the rats were sacrificed and their brains were preserved for later 
analysis.

The researchers wanted to know if animals exposed to MDMA during early 
brain development would show the same pattern of damage to 
neurotransmitters that has been shown in adult animals exposed to MDMA. 
They did not. "

This was a surprise because we didn't find the same damage to 
neurotransmitters as was found in previous studies of animals exposed to 
MDMA as adults," says Dr. Vorhees. "Yet, the animals in the current study 
still show cognitive impairment, as demonstrated by their performance on 
the learning and memory trials." He hypothesizes that a different mechanism 
is at work in animals exposed to MDMA during brain development that later 
affects their memory and learning ability. Future research will focus on 
identifying this mechanism. Dr. Frankenheim points out that this research 
is a warning that what is happening in animals may also happen with people.

"The work of determining what drugs of abuse do to fetuses when the mother 
takes them is very difficult. It is not yet known whether human fetuses 
exposed to MDMA will develop persistent memory and learning problems. 
However, these findings in rats raise the concern that MDMA may pose a 
previously unrecognized risk to the developing human brain," he says.

Future research will involve determining the effects of MDMA exposure at 
earlier points in fetal development, such as during the period 
corresponding to the first trimester in humans, when drug exposure is more 
likely for women who may not yet be aware that they are pregnant. The first 
trimester is also the developmental period when humans are most sensitive 
to neurotoxins.
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