Ecstasy Can Trigger Heart Attacks In Users

The illegal drug MDMA (Methylene 3, 4 dioxy-methamphetamine) more commonly known as "Ecstasy" or "XTC," can trigger heart attacks, according to a case report in the December issue of Annals of Emergency Medicine. The case report describes a 27-year-old male who sought treatment at an emergency department after experiencing symptoms of chest tightness and discomfort for three hours.

The man reported that prior to experiencing these symptoms he drank a bottle of whisky and taken half of a pill of MDMA. He was diagnosed and treated in the emergency department for acute myocardial infarction as a result of MDMA use. This is only the second case reported showing evidence that MDMA can cause heart attacks similar to those caused by amphetamines, according to the report's authors. (Methylene 3, 4 Dioxy-Methamphetamine-Induced Acute Myocardial Infarction, p. 759)

The role of MDMA on coronary vessels is not well documented. However, the case report's authors from the National Taiwan University Hospital in Taipei, Taiwan, speculate that MDMA-related heart attacks may be similar to those caused by cocaine or amphetamine use. Other studies have found cocaine and amphetamines promote coagulation of blood that can lead to blood clots in the arteries, which can cause heart attacks.

Physicians in the emergency department should become familiar with this drug because of its emerging trend toward its use, advise the case report's authors. Although it was once thought that the drug does not cause dependency and adverse side effects, this belief has been overturned by many reports of side effects in recent literature, the report further explains.

Annals of Emergency Medicine is the peer-reviewed journal of the American College of Emergency Physicians, a national medical specialty organization with nearly 23,000 members.

Brain's 'Master Molecule' Produces Same Behavior In Mice From Three Different Psychostimulant Drugs

A mouse study reported in this week's Science magazine shows that three drugs, each acting on a different chemical transmitter in the brain, all produce the same schizophrenia-like symptoms by acting on a single "master molecule" in the brain.

The findings, reported by researchers at Rockefeller University with collaboration from three pharmaceutical and biotech companies, provides, for the first time, a cellular model detailing how this crucial protein, known as DARPP-32, interacts with multiple neurotransmitter systems to produce behavior.

The scientists demonstrate that DARPP-32 acts like the thin neck in an hourglass, through which all signals taken into a nerve cell must pass and be processed, producing a wide variety of biochemical reactions. In this case, three different drugs of abuse, LSD, PCP ("angel dust") and amphetamine, work on three different neurotransmitters, serotonin, glutamate, and dopamine, respectively. All three drugs, which are classified as psychotomimetics or psychostimulants, are processed within the DARPP-32 hourglass neck through the same pathway, thus producing very similar physiological symptoms.

"For the first time, we can explain through a molecular model why these drugs all produce the same kind of behavioral symptoms," says the study's first author, Per Svenningsson, M.D., Ph.D., a research assistant professor in the Laboratory of Molecular and Cellular Neuroscience, headed by Paul Greengard, Ph.D.

Clinically, the study does not suggest that DARPP-32 is the root cause of schizophrenia, but it does provide new avenues in which to treat the disease, says Greengard, Vincent Astor Professor at Rockefeller and the study's principal investigator.

By experimentally blocking the function of one of the 205 amino acids that make up DARPP-32, the research team was able to abolish the effects of the drugs, all of which have long been known to produce schizophrenia-like behavior in both mice and humans.

"This is remarkable because it shows that a single amino acid on a single protein, by being altered, can abolish the effects of these psychotomimetic drugs on behavior," says Greengard, who shared the 2000 Nobel Prize in Medicine or Physiology for his work on neurotransmitters and DARPP-32. "The research certainly indicates new targets for the development of antipsychotic drugs."

The study also answers a long-standing debate in psychiatry as to which neurotransmitter is primarily responsible for schizophrenia, says Greengard, because researchers have known that drugs like LSD, PCP and amphetamines, which act on different transmitters, create the same psychoses as seen in schizophrenia.

"It turns out everyone was right, because each of these drugs work on a common pathway regulated by DARPP-32," says Greengard.

Previous research by Svenningsson and Greengard also has demonstrated that DARPP-32 regulates the actions of medications such as Prozac, to treat depression, as well as drugs of abuse such as cocaine, opiates and nicotine.

"We have begun to believe that DARPP-32 is really a master molecule that integrates information coming in from all parts of the brain and is involved in mediating and regulating the actions of many, many neurotransmitters," says Greengard.

The investigators knew that, like many such proteins, DARPP-32 can be activated by the addition of a phosphate molecule (a process called "phosphorylation") or by removal of a phosphate molecule ("dephosphorylation") on specific amino acid sites.

In the findings reported in Science, the Rockefeller team found that DARPP-32 was phosphorylated or dephosphorylated at three sites by the studied psychotomimetics, in a pattern that worked together to inhibit an enzyme downstream of DARPP-32 called protein phosphatase-1 (PP-1). PP-1 helps regulate its own series of biochemical reactions that lead to physiological responses.

In order to understand the precise functional importance of these three phosphorylation sites, the scientists created a series of "knockin" mice, in which each of these sites on the DARPP-32 protein were mutated. The behavioral responsively to LSD, PCP and amphetamine were thereafter compared between these mutant mice and normal mice. It turned out that single mutations in the amino acid sequence of DARPP-32 virtually abolished the behavioral actions of the psychotomimetics.

Schizophrenia-like symptoms such as repetitive movements and sensory perception defects induced by the psychotomimetics were strongly attenuated in two of the three different mutant mouse lines, implicating a critical involvement of two distinct, but interacting, phosphorylation sites of DARPP-32 in the actions of LSD, PCP and amphetamine, says Svenningsson.

Ongoing research is aimed at further understanding how DARPP-32 can process a wide variety of neurotransmitters that affect behavior, he says. "This master molecule seems to be involved in many behaviors, including those related to mood and the way we perceive the world," says Svenningsson.

Co-authors of the study, funded by the National Institutes of Health, include researchers from Rockefeller University (Robert Carruthers and Ilan Rachleff), Eli Lilly and Company (Eleni Tzavara, David McKinzie, George Nomikos), Lexicon Genetics, Inc. (Sigrid Wattler and Michael Nehls) and Intra-Cellular Therapies (Allen Fienberg). Fienberg also is affiliated with Rockefeller University.

Steroid Use Causes Long-term Agression, Northeastern University Report Indicates

 BOSTON, Mass. (11-20-03) -– With the recent revelations about steroid use in Major League Baseball and the bust last week of several Oakland Raiders players for drug abuse, Northeastern University psychology professor Richard Melloni, who studies the link between steroid use and aggression, has recently found evidence that use of anabolic steroids may have long-term effects on behavior and aggression levels well after they stop abusing these performance enhancing drugs.

With funding from the NIH (recently extended through 2008), Melloni and doctoral student Jill Grimes have been studying how steroids used during adolescence may permanently alter the brain's ability to produce serotonin. In their experiments, adolescent Syrian hamsters – given their similar brain circuitry to human adolescents – were administered doses of anabolic steroids and then measured for aggressiveness over certain periods of time.

The researchers initially hypothesized that steroid use during adolescence might permanently alter the brain's chemistry and a person's tendency toward aggression long after use has stopped. Their most recent findings, published this week in Hormones and Behavior, enabled them to confirm this hypothesis and conclude that there is indeed a lengthy price – namely long-term aggression – to pay for drug abuse even after the ingestion of steroids ceases.

"We know testosterone or steroids affect the development of serotonin nerve cells, which, in turn, decreases serotonin availability in the brain," Melloni says. "The serotonin neural system is still developing during adolescence and the use of anabolic steroids during this critical period appears to have immediate and longer-term neural and behavioral consequences. What we know at this point is that aggressiveness doesn't simply cease after the ingestion of steroids does."

Based on this research, Melloni also believes that athletes who abuse steroids may also be inclined toward aggressive behavior long after their drug abuse – and musculature – have waned.

Promising Drug Proves Ineffective As Treatment For Hearing Loss

NewsPsychology (Oct. 8, 2003) — Researchers have demonstrated that Methotrexate, a promising drug to treat hearing loss in patients with autoimmune inner ear disease (AIED), proved no more effective than placebo in a recently concluded four-year study.

In findings published in the October 8, 2003 issue of the Journal of the American Medical Association (JAMA), a team headed by University of California, San Diego (UCSD) Professor and Chief of Otolaryngology Head and Neck Surgery, Jeffrey Harris, M.D., also noted that the steroid Prednisione proved very effective in both stabilizing and helping over 57% of the AIED patients regain hearing.

“AIED is a rapidly progressive form of sensorineural hearing loss. If left untreated or treated inadequately, AIED can result in profound deafness,” says Harris. “We’ve known for some time that steroids are effective in improving hearing loss in AIED.”

However, he noted, the many side effects associated with maintaining prolonged steroid therapy has led to the search for more effective drugs to treat this condition over the long term. And, once the steroids are withdrawn, the hearing loss may reoccur. Methotrexate has been considered a promising drug to treat AIED, due to its long track record as an effective anti-inflammatory, says Harris, improving patients with rheumatoid arthritis, an autoimmune disease that affects the body’s joints. Since AIED is also an autoimmune condition, Harris says researchers hoped the drug would have the same therapeutic effect.

AIED starts with the rapid appearance of bilateral, fluctuating and progressive, asymmetrical sensorineural hearing loss. Patients show hearing loss and usually tinnitus. Several blood tests are now being tested to identify patients with AIED. Approximately two-thirds of patients exhibit this autoimmune disease in their ears. In the other third, patients may have some of the well-known rheumatic diseases occurring concurrently with the hearing loss.

“In earlier studies where Methotrexate was used to treat AIED, the initial results appeared positive. The current study was designed to determine in a controlled, double-blind fashion if Methotrexate could maintain the hearing improvement achieved initially with Prednisone,” Harris says.

The study enrolled 116 patients with AIED, treating each of them with one month of high dose Prednisone. At the end of the first phase, 67 who showed significant hearing improvement were randomized to receive either Methotrexate or placebo. Prednisone was slowly tapered in both groups over a 3-month period while the Methotrexate and placebo doses were increased.

The results showed that Methotrexate was no more effective than the placebo in maintaining the hearing gain achieved with Prednisone. Of the 67 patients who went on to receive Methotrexate or placebo, 61 were disqualified from continuing the study due to further hearing losses.

Of the 116 patients who received the initial high dose steroids, 63% responded to Prednisone in one ear while 37% responded in both ears, and the researchers observed that long-term Prednisone was well tolerated under the close management of the treating physicians involved in this study.

Harris says the results underscore the importance of well-controlled studies to test the efficacy of drugs in the treatment of AIED, adding it also demonstrates the urgent need to discover more effective and lasting treatments for this condition that usually leads to acute deafness.

###

The study published in JAMA was sponsored by the National Institute on Deafness and Communication Disorders. Co-authors were Michael H. Weisman, M.D., Cedars-Sinai Medical Center, Los Angeles; Jennifer M. Derebery, M.D., and Ralph A. Nelson, M.D., House Ear Institute, Los Angeles; Mark A. Espeland, PhD, Wake Forest University, Winston-Salem, NC; Bruce J. Gantz, M.D., University of Iowa, Iowa City; A. Julianna Gulya, M.D., National Institute on Deafness and Other Communication Disorders, Bethesda, MD; Paul E. Hammerschlag, M.D., New York University, NYC; Maureen Hannley, PhD, American Academy of Ototlaryngology-Head & Neck Surgery, Alexandria, VA; Gordon B. Hughes, M.D., The Cleveland Clinic, Cleveland, OH, Richard Moscicki, M.D., Massachusetts General Hospital, Boston, MA; John K. Niparko, M.D., Johns Hopkins University, Baltimore, MD; Steven D. Rauch, M.D., Massachusetts Eye and Ear Infirmary, Boston, MA; Steven A. Telian, M.D., University of Michigan, Ann Arbor, MI; and Patrick E. Brookhouser, M.D., Boystown National Research Hospital, Omaha, NE.

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The above story is reprinted (with editorial adaptations by newsPsychology staff) from materials provided by University Of California – San Diego.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of NewsPsychology or its staff.

Taking Ecstasy During Pregnancy May Cause Brain Damage, Behavior Problems In Babies

Women who take the drug Ecstasy in their first trimester of pregnancy may be putting their unborn child at risk for brain damage, according to a study published in the September issue of the journal Neurotoxicity and Teratology.

Jack W. Lipton, PhD, a neuroscientist at Rush-Presbyterian-St. Luke's Medical Center in Chicago, demonstrated that fetal exposure in rats to the drug Ecstasy during a period analogous to the first trimester in humans causes changes in the young rat's brain chemistry and behavior. The study was funded in part by the National Institute on Drug Abuse (NIDA). Ecstasy also is known as MDMA or 3,4-methylenedioxymethamphetamine.

"The limited data that exist suggest that women who use Ecstasy stop taking it when they learn they are pregnant," says Dr. Nora D. Volkow, director of the NIDA. "But many of the animal studies that linked this drug to neurological changes and learning impairments were conducted in situations analogous to the third trimester in humans. Thus, this study sought to investigate a more true-to-life situation by looking at neurobiological changes caused by Ecstasy early in pregnancy."

The researchers injected the drug twice daily from day 14 through day 20 of pregnancy. An equal number of pregnant rats were given sham injections of saline twice daily during the same period as a placebo. The most striking finding was that 21-day-old Ecstasy exposed rats had a 502% increase in the number of dopamine neuron fibers in the frontal cortex as compared to controls. The frontal cortex is important in planning, impulse control and attention.

Similar but smaller increases in dopaminergic fiber density were also evident in the striatum — an area involved in movement and reward and the nucleus accumbens — the primary site of action of rewarding stimuli. The investigators believe that this hyperinnervation is either due to MDMA-induced reductions in the normal cell loss that occurs during fetal development, or MDMA-induced increases in chemicals known as trophic factors which can mediate growth and survival of brain cells.

Lipton and his colleagues also found that behavioral changes were evident as well. When 21-day-old rats exposed to Ecstasy in the womb were placed in a new environment away from their littermates, they spent significantly more time exploring and did not habituate as easily to the new environment. Such findings suggest that the Ecstasy exposed rats may have learning or attention deficits or alterations in their anxiety levels. Another possibility is that they are simply hyperactive as a result of their in utero exposure.

"Our findings show that exposing rats to Ecstasy at a time of prenatal development that correlates with the first trimester in humans results in lasting changes in brain chemistry and behavior," notes Lipton. "This research warrants the continued monitoring of children exposed to this drug."

Rush-Presbyterian-St. Luke's Medical Center is an academic medical center that encompasses the 824-bed Presbyterian-St. Luke's Hospital (including Rush Children's Hospital), the 110-bed Johnston R. Bowman Health Center and Rush University. Rush University, with more than 1,270 students, is home to one of the first medical schools in the Midwest, one of the nation's top-ranked nursing colleges, as well as graduate programs in allied health and the basic sciences. Rush is noted for bringing together clinical care and research to address major health problems, including arthritis and orthopedic disorders, cancer, heart disease, mental illness neurological disorders and diseases associated with aging.

Rat Study Shows Exposure To Ecstasy Early In Pregnancy Induces Brain, Behavior Changes

Researchers at Rush Presbyterian-St. Luke's Medical Center in Chicago have shown that 21-day-old rat pups exposed in the womb to the drug MDMA (3,4-methylenedioxymethamphetamine, often called Ecstasy) during a period corresponding to the first trimester in human pregnancy exhibit changes in brain chemistry and behavior.

"Existing data suggest that most women who use MDMA stop taking it when they learn they are pregnant," says NIDA Director Dr. Nora D. Volkow. "But the animal studies that linked this drug to neurobiological changes and learning impairments were conducted in situations analogous to the third trimester in humans. This study sought to investigate a more true-to-life situation by looking at the consequences of Ecstasy exposure early in pregnancy."

The study, funded in part by NIDA, was published August 29 on the journal of Neurotoxicology and Teratology Web site.

Dr. Jack W. Lipton, doctoral student James Koprich, and their colleagues injected 8 pregnant rats twice daily with MDMA from day 14 through day 20 of pregnancy, a period corresponding to the first 3 months of human fetal development. The scientists injected saline twice daily during the same period to another 8 pregnant rats. The researchers examined brain tissue of the rat pups when they were 21 days old. A 21-day-old rat pup is roughly equivalent to a 2- to 6-year-old child.

"Our most striking finding was that 21-day-old MDMA-exposed pups had a 502-percent increase in the number of dopamine neuron fibers in the frontal cortex compared with control animals," notes Dr. Lipton. Abnormal or overly numerous connections in the frontal cortex may result in aberrant signaling there, possibly resulting in abnormal behavior.

Dopamine is a brain chemical that carries or transmits messages between nerve cells. It is involved in a variety of motivated behaviors, such as eating, sex, and drug-taking. The frontal cortex is important in planning, impulse control, and attention.

The scientists also saw similar but smaller increases in dopamine fibers in the striatum (a brain area involved in locomotion and reward) and the nucleus accumbens (the primary site of action of rewarding stimuli).

MDMA-exposed pups also showed modest decreases in dopamine metabolism in brain structures that play key roles in reward, addiction, learning, and movement. There also was a reduction in serotonin metabolism. Serotonin also is a brain chemical that helps to regulate mood, sleep, and appetite. Interestingly, the reductions in dopamine and serotonin metabolism that were observed in the nucleus accumbens were evident in male, but not female, pups suggesting sex differences in vulnerability to some of MDMA's prenatal effects.

The rat pups also exhibited behavioral changes. When the Ecstasy-exposed pups were placed in a new environment away from their littermates, they spent significantly more time exploring, signifying they did not adjust as easily to the new environment as the control animals.

"Our findings show that exposing rats to Ecstasy at a time of prenatal development that correlates with the first trimester in humans may result in lasting changes in brain chemistry and behavior," notes Dr. Lipton. "Our findings also suggest that MDMA exposure may result in hyperactivity or deficits in attention or learning. Further research is needed to learn more about the effects of prenatal exposure to this drug."

The National Institute on Drug Abuse is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports more than 85 percent of the world's research on the health aspects of drug abuse and addiction. The Institute carries out a large variety of programs to ensure the rapid dissemination of research information and its implementation in policy and practice. Fact sheets on the health effects of drugs of abuse and information on NIDA research and other activities can be found on the NIDA home page at http://www.drugabuse.gov

Research Links Adolescent Steroid Use To Reduction In Serotonin, Altered Signaling

BOSTON, Mass. — With more than one in ten boys admitting to using steroids, muscle- and strength-enhancing drug use among teenagers has caused considerable concern among parents and researchers over the past decade, but until now, the longer-term physiological and neurological effects of its use on the developing brain have not been fully examined. Now, new research from Northeastern University, published in the latest issue of the journal Pharmacology, Biochemistry and Behavior, documents the link between adolescent anabolic steroid use and aggression and partly associates the increases in aggression with deficits in the brain"s serotonin system. The study will examine longer-term deficiencies of serotonin levels in the brain as a result of damage from steroid use, suggesting that a tendency toward aggression and impulsiveness may actually linger long after both the steroid use and the muscles and strength developed have waned.

With funding from the National Institute of Health, Northeastern University psychology professor Richard Melloni and graduate student Jill Grimes examined the phenomenon of long-term steroid use through a series of experiments on groups of adolescent male Syrian hamsters. During adolescence, this particular breed of hamster displays a natural form of territorial aggression, has similar neurological circuitry to human beings and similar aggression and dominance patterns during its adolescent years, making it a natural model for neurological and behavioral experiments.

During the first experiment, the researchers administered a "high dose" of anabolic steroids to adolescent hamsters over the course of a month, a period corresponding to five years repeated dosage in human adolescents. Those hamsters given steroids were, as other studies have shown, more aggressive than those not treated with steroids.

In the second stage of the experiment, the researchers administered fluoxtine (Prozac), commonly used in treating depression in humans by encouraging the presence of serotonin (the "feel good" receptor), to the hamsters treated with chronic levels of steroids, and found that the previously aggressive tendencies were notably decreased. As in humans, aggressions were mellowed in the presence of Prozac, or serotonin.

Finally, the brains of the anabolic steroid-treated hamsters were examined under a microscope to determine the effect the drugs have on the developing nervous system. In those animals exposed to steroids, significantly lower levels of serotonin were present in the neural connections in their brains, particularly in areas related to aggression and violence.

Melloni and his students plan to conduct a series of follow-up experiments to examine whether the observed serotonin deficits in light of steroid use cause permanent and irreversible damage to the brain and how the neural abnormalities of adolescent anabolic steroid use may affect humans into adulthood. The researchers hypothesize that steroid exposure during adolescence decreases naturally occurring levels of the feel good receptor serotonin particularly in the hypothalamus, the area of the brain pinpointed for aggression and violence, and they plan to conduct a series of follow-up experiments to examine whether the serotonin deficiencies linger and what the longer-term abnormalities of adolescent steroid use actually are into adulthood.

"We know testosterone or steroids affect the development of serotonin nerve cells, which, in turn, decreases serotonin availability in the brain," Melloni said. "The serotonin neural system is still developing during adolescence and the use of anabolic steroids during this critical period appears to have immediate neural and behavioral consequences. Further research will allow us to determine whether or not these deficits are present into adulthood."

Continued steroid use during adolescence is linked not only to aggression and violence, but to a host of physiological problems, including liver diseases, problems with physical growth and development, and sexual dysfunction. Melloni notes that there is currently no long-term understanding of the effects of certain drug use on young people, and that drugs like Ritalin, among others, have no research indicating what aftereffects remain well into adulthood.

Steroid use, he says, is considerably on the rise, with more than ten percent of boys and three percent of girls admitting to regular use.

"Given the fact that we know so little about steroid"s long-term effects, the prospect of results from our research will be doubtlessly interesting and perhaps even frightening," Melloni said. "Perhaps through this sort of research we"ll be able to decrease the popularity of steroid use among teenagers."

Northeastern University, a private research institution located in Boston, Massachusetts, is a world leader in practice-oriented education. Building on its flagship cooperative education program, Northeastern links classroom learning with workplace experience and integrates professional preparation with study in the liberal arts and sciences. For more information, please visit http://www.northeastern.edu

Methamphetamine Drastically Increases Virus Ability To Replicate In Brain Tissue

COLUMBUS, Ohio – A controversial research study here has found that exposing cells infected with feline immunodeficiency virus – a surrogate for HIV – to methamphetamine increases those cells' ability to replicate the deadly virus as much as 15-fold.

The finding, if confirmed by ongoing animal studies, could answer important questions about how lentiviruses such as FIV and HIV can gain a foothold in the brain. That knowledge is vital in slowing or lessening the dementia that often accompanies AIDS and similar diseases.

Ohio State University researchers reported this finding in a paper to be published in the next issue of the Journal of NeuroVirology.

The paper also reports that before a nerve cell can become infected with the virus, it must be associated with a specific type of lymphocyte, or immune cell. Lastly, the researchers discovered that once the virus infects the cells, it mutates into a form that no longer needs this immune-cell association to reproduce.

"We found that after about two weeks of chronic methamphetamine exposure, the ability of these infected cell lines to mass-produce virus increases dramatically," explained Michael Podell, a professor of veterinary clinical sciences and neurosciences.

The concentration of the drug the cells were exposed to was equal to an average level of methamphetamine in an adult abuser's bloodstream, Podell said.

Like HIV, or human immunodeficiency virus, FIV belongs to a family of pathogens called lentiviruses. Lentivirus infections are particularly problematic since these viruses can escape detection by a healthy immune system, mutate quickly and lead to life-long infections in the host, Podell said.

FIV is one of the principal stand-ins for studies of HIV since the viruses are closely related. Studies of this kind using HIV cannot be done safely or ethically in humans.

Viruses spread within the body by first breaching the cell wall and taking up residence within the cellular environment. Once there, the virus begins replicating, or reproducing, until its numbers are so great the cell literally bursts, spreading the virus to nearby cells and throughout the bloodstream.

The Ohio State researchers focused on astrocytes, nerve cells that may make up as much as half of the brain but which for a long time were thought to play a minimal role. Recent research has shown that astrocytes are among the most important cells in the brain and may play a key role in immunity. While scientists had known that FIV and HIV could infect astrocytes, they believed the infection was merely a latent one with the virus remaining almost in dormancy.

Podell, along with colleagues Lawrence Mathes, professor of veterinary biosciences and director of OSU's Center for Retroviral Research, and Mikhail A. Gavrilin, a research scientist in the Department of Veterinary Clinical Sciences, found that FIV is only able to infect astrocytes when they are associated with a peripheral blood mononuclear cell, or PBMC.

A receptor molecule on the astrocyte's cell membrane allows the virus to enter the astrocyte, the researchers found. Both FIV and HIV are able to use the same receptor – CXCR4 – on astrocytes and on immune system cells. They believe CXCR4 may be the principal receptor for all lentiviruses on astrocytes.

The researchers noticed that once it had infected the astrocytes, the virus began to rapidly reproduce – an observation that was contrary to scientists' belief that FIV resulted only in a latent infection. "We found that the reason the virus multiplies so rapidly is that it mutates into a different strain," Podell said, one that isn't dependent on the presence of the other PBMC cells.

This virus strain – MD-A – appears to be completely independent of any immune system interaction. "That means that any drugs intended to interfere with, or influence the immune system may have absolutely no effect on the astrocyte infection in the brain," Podell said.

The experiments with methamphetamine exposure to the cells were surprising to the researchers.

"We found that if you treat these astrocyte cell lines with methamphetamine at the time that they are infected with FIV, and if you continuously expose them to the drug, you can see as much as a 15-fold increase in viral replication," Podell said.

"You can basically take this cell that normally has a limited ability to consistantly replicate virus and just dramatically turn it on, simply by adding methamphetamine."

The research team is now analyzing data obtained from as series of experiments that used cats as an animal model. If the findings are corroborated in the animals, Podell and his colleagues will try to unravel the precise mechanisms that are controlling FIV infection in these cells.

"The most difficult issue lies ahead, and that is understanding what mechanism is occurring and potentially discovering how to stop or block viral infection and replication in this environment," he said.

The project was supported by grants from the National Institute on Drug Abuse and the National Institutes of Health.

Ecstasy Link To Long-Term Brain Damage

Disturbing evidence is emerging that the increasingly popular drug ecstasy can be linked to users suffering long-term brain damage.

University of Adelaide researchers have found that ecstasy taken on a few occasions could cause severe damage to brain cells, with the potential to cause future memory loss or psychological problems.

Dr Rod Irvine, an internationally regarded ecstasy expert from the University's Department of Clinical and Experimental Pharmacology, says with 7% of 17-year-olds reporting use of ecstasy, major health problems could be expected in the future.

"For many years it has been known from animal experiments that small doses of ecstasy-even if only taken on only a few occasions-can cause severe damage to certain brain cells," he says. "More recently, evidence has started to accumulate suggesting that this damage may also occur in humans. Brain scans and psychological assessment of ecstasy users has been used to obtain this information.

"If our suspicions are proved correct, it will mean many of our young people will have memory loss or psychological problems in the future."

Dr Irvine's research on brain damage caused by ecstasy shows that the drug seems to work mainly through its effects on one type of brain cell, and even through one molecule in those cells. It also seems likely that the way the body reacts chemically to ecstasy is important in producing adverse effects, as is the surrounding temperature, which can lead to users overheating.

Adelaide's reputation as having the highest per capita death rate from ecstasy in Australia-and perhaps even the world-forms another component of Dr Irvine's research.

Dr Irvine is looking at the shorter-term consequences of ecstasy "overdoses", and has established that the high rate of death is due to a different strain of ecstasy appearing on the Adelaide market in the mid1990s.

"Normal" ecstasy contains the pharmacological ingredient known as MDMA as its main ingredient, but the Adelaide strain often contained no MDMA but rather a more potent chemical known as PMA.

"PMA hasn't been around since the early 1970s when it was responsible for the deaths of several people in Ontario, Canada, and now it's reappeared here in Adelaide," Dr Irvine says. "We don't know where the PMA came from, but we do know that it has been prevalent in Adelaide since the mid 1990s."

Brain Shows Ability To Recover From Some Methamphetamine Damage

UPTON, NY — A new brain-imaging study at the U.S. Department of Energy's Brookhaven National Laboratory indicates that some of the damage caused by methamphetamine — a drug abused by ever-increasing numbers of Americans — can be reversed by prolonged abstinence from the drug. The results appear in the December 1, 2001 issue of The Journal of Neuroscience.

"Methamphetamine is a particularly problematic, highly addictive drug," said Nora Volkow, who led the study with Linda Chang. Their team had previously shown that methamphetamine abusers have significantly depleted levels of dopamine transporters. These proteins, found on the terminals of some brain cells, recycle dopamine, a brain chemical associated with pleasure and reward and also essential for movement. The study also found that meth abusers had impaired cognitive and motor function (see http://www.bnl.gov/bnlweb/pubaf/pr/bnlpr030101.htm).

"These changes could mean that meth abusers would be predisposed to such neurodegenera-tive disorders as Parkinson’s disease, which is also characterized by problems with dopamine and motor function," Volkow said. "It depends in part on whether the damage is reversible."

To help answer this question, Volkow and her team used positron emission tomography, or PET scanning, to measure the level of dopamine transporters in methamphetamine abusers after varying periods of abstinence. One group of 12 methamphetamine abusers was scanned within 6 months of taking the drug, and, for 5 of these subjects who managed to stay drug-free, the scan was repeated after 9 months of abstinence. Another group of 5 methamphetamine abusers was studied only after 9 months of abstinence. All subjects were compared with normal controls.

For each scan, each study volunteer was given an injection carrying a radiotracer, a radioactive chemical "tag" designed to bind to dopamine transporters in the brain. The researchers then scanned the subjects' brains using a PET camera, which picks up the radioactive signal of the tracer bound to the transporters. The strength of the signal indicates the number of transporters.

The scientists also looked for improvements in cognitive and motor function after abstinence by administering a battery of neuropsychological tests. These included tests of fine and gross motor function and tests of attention and memory.

The main finding was that, in methamphetamine abusers who were able to stay drug-free for at least 9 months, dopamine transporter levels showed significant improvement, approaching the level observed in control subjects. In abusers studied within 6 and after 9 months, the longer the period between the first and second evaluation, the larger the increase in dopamine transporter levels. Cognitive and motor function showed a trend toward improvement on some tests, but these changes were not statistically significant.

"The increase in dopamine transporter levels with prolonged abstinence indicates that the terminals of dopamine-secreting cells, which are thought to be damaged by methamphetamine abuse, are able to regenerate," Volkow said. Another possibility is that other, undamaged terminals are able to branch out and make up for the loss.

"These findings have implications for the treatment of methamphetamine abusers because they suggest that protracted abstinence and proper rehabilitation may reverse some of the meth-induced alterations in dopamine cells," Volkow said. "Unfortunately, we did not see a parallel improvement in function."

The recovery of dopamine transporters may not have been sufficient to completely make up for the damage to the dopamine terminals, she suggested. Additionally, other systems necessary for neuropsychological function might also be damaged by the drug — and less able to recover. Also, Volkow noted, the sample sizes were small. "Further study in larger samples is required to assess whether recovery of dopamine transporters with protracted abstinence is associated with recovery of neuropsychological function," she said.

This work was funded by the U.S. Department of Energy, which supports basic research in a variety of scientific fields; the National Institute on Drug Abuse; the National Institutes of Health; and the Office of National Drug Control Policy.

The U.S. Department of Energy's Brookhaven National Laboratory (http://www.bnl.gov) conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies. Brookhaven also builds and operates major facilities available to university, industrial, and government scientists. The Laboratory is managed by Brookhaven Science Associates, a limited liability company founded by Stony Brook University and Battelle, a nonprofit applied science and technology organization.