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Hope for treating relapse to methamphetamine abuse
November 13, 2008Vigabatrin shown to block reinstatement of drug-seeking behavior
UPTON, NY - A new study at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory suggests that vigabatrin (a.k.a. gamma vinyl-GABA, or GVG) blocks drug-seeking behavior in animals previously trained to associate methamphetamine with a particular environment. Specifically, animals pre-treated with vigabatrin lost interest in spending time in a location where they had previously been given methamphetamine. The results will appear in the February 2009 issue of Synapse, now available online.
"Reinstatement of drug-seeking behavior after an extended period of abstinence is the number-one cause of drug-addiction relapse," said Brookhaven neuroanatomist Stephen Dewey, who led the research team. "This animal study suggests that vigabatrin could potentially prevent human methamphetamine addicts from relapsing."
According to the National Institute on Drug Abuse, methamphetamine is a very addictive stimulant that is quickly becoming an American public health epidemic. There is currently no effective treatment for methamphetamine addiction.
Vigabatrin is a pharmaceutical agent first tested as a possible treatment for a variety of addictions in animal studies led by Dewey at Brookhaven Lab (http://www.bnl.gov/CTN/GVG/). It is the only drug that has been shown to block any behavior associated with methamphetamine use, and is currently being tested by Catalyst Pharmaceutical Partners (http://www.catalystpharma.com/) for safety and efficacy against cocaine and methamphetamine addiction in humans in Phase II clinical trials across the U.S.
"In human drug abusers, many things can cause relapse - exposure or access to drugs, environmental cues that trigger thoughts of the drug, or stress," said Dewey. "If vigabatrin can prevent relapse, it could have a huge impact by helping drug abusers regain control over their lives."
In the current study, rats were first put through a series of conditioning tests that taught them to expect methamphetamine in one chamber of a three-chamber apparatus and saline solution in another chamber. The researchers then allowed the rats to roam freely among the three chambers. If the rats spent the majority of their time in the chamber where they had been given methamphetamine, the scientists knew they had established a "conditioned place preference."
Once this preference was established, the researchers extinguished it by giving the rats saline injections in both chambers, again allowing the animals to have free access to all chambers until the rats had no preference for the previously methamphetamine-associated chamber for at least six consecutive days.
Once extinguished, however, it is possible for a conditioned preference to be reinstated - just as it is possible for a recovered drug addict to relapse. To reinstate the place preference in this experiment, Brookhaven scientists injected the rats with methamphetamine in the neutral chamber. Immediately, rats went to the chamber where they had received methamphetamine and remained there for the duration of the exposure period.
Then, once the reinstatement of a preference was clearly demonstrated, the researchers tested the effectiveness of vigabatrin at blocking it. They pre-treated animals with vigabatrin two-and-a-half hours before giving them another priming dose of methamphetamine followed by free access to all three chambers. When pre-treated with vigabatrin, the rats no longer showed any preference for one chamber over another.
Dewey's group is now conducting studies to examine whether GVG will also block an environmental cue previously shown to produce relapse to drug-seeking behavior.
"These studies have wide implications for addressing the number-one cause of relapse to drug seeking behavior. If we can successfully block drug-induced reinstatement, then our ability to block environmental cue-induced relapse is significantly enhanced," Dewey said.
DOE/Brookhaven National Laboratory
According to the National Institute on Drug Abuse, methamphetamine is a very addictive stimulant that is quickly becoming an American public health epidemic. There is currently no effective treatment for methamphetamine addiction.
Vigabatrin is a pharmaceutical agent first tested as a possible treatment for a variety of addictions in animal studies led by Dewey at Brookhaven Lab (http://www.bnl.gov/CTN/GVG/). It is the only drug that has been shown to block any behavior associated with methamphetamine use, and is currently being tested by Catalyst Pharmaceutical Partners (http://www.catalystpharma.com/) for safety and efficacy against cocaine and methamphetamine addiction in humans in Phase II clinical trials across the U.S.
"In human drug abusers, many things can cause relapse - exposure or access to drugs, environmental cues that trigger thoughts of the drug, or stress," said Dewey. "If vigabatrin can prevent relapse, it could have a huge impact by helping drug abusers regain control over their lives."
In the current study, rats were first put through a series of conditioning tests that taught them to expect methamphetamine in one chamber of a three-chamber apparatus and saline solution in another chamber. The researchers then allowed the rats to roam freely among the three chambers. If the rats spent the majority of their time in the chamber where they had been given methamphetamine, the scientists knew they had established a "conditioned place preference."
Once this preference was established, the researchers extinguished it by giving the rats saline injections in both chambers, again allowing the animals to have free access to all chambers until the rats had no preference for the previously methamphetamine-associated chamber for at least six consecutive days.
Once extinguished, however, it is possible for a conditioned preference to be reinstated - just as it is possible for a recovered drug addict to relapse. To reinstate the place preference in this experiment, Brookhaven scientists injected the rats with methamphetamine in the neutral chamber. Immediately, rats went to the chamber where they had received methamphetamine and remained there for the duration of the exposure period.
Then, once the reinstatement of a preference was clearly demonstrated, the researchers tested the effectiveness of vigabatrin at blocking it. They pre-treated animals with vigabatrin two-and-a-half hours before giving them another priming dose of methamphetamine followed by free access to all three chambers. When pre-treated with vigabatrin, the rats no longer showed any preference for one chamber over another.
Dewey's group is now conducting studies to examine whether GVG will also block an environmental cue previously shown to produce relapse to drug-seeking behavior.
"These studies have wide implications for addressing the number-one cause of relapse to drug seeking behavior. If we can successfully block drug-induced reinstatement, then our ability to block environmental cue-induced relapse is significantly enhanced," Dewey said.
DOE/Brookhaven National Laboratory
Methamphetamine Current Events and Methamphetamine News RSSLocal health investigation sheds light on gastroschisis birth defect
Results of an investigation conducted by University of Nevada, Reno researchers, public health officials and area physicians published this week in the Archives of Pediatrics & Adolescent Medicine, indicate that Washoe County experienced a cluster of a particular birth defect, gastroschisis, during the period April 2007 - April 2008.
Wastewater used to map illicit drug use
A team of researchers has mapped patterns of illicit drug use across the state of Oregon using a method of sampling municipal wastewater before it is treated.
Risky sexual behavior among male clients of Tijuana sex workers heightens risk of HIV transmission
A study by a bi-national team of global health researchers at the University of California, San Diego School of Medicine, examining HIV infection among male clients of female sex workers in Tijuana, has found that over half of male clients had recently had unprotected sex.
Brain protein central to both Parkinson's, drug addiction identified
Scientists have identified a protein that appears not only to be central to the process that causes Parkinson's disease but could also play a role in muting the high from methamphetamine and other addictive drugs.
Brain protein central to both Parkinson's, drug addiction identified
Scientists have identified a protein that appears not only to be central to the process that causes Parkinson's disease but could also play a role in muting the high from methamphetamine and other addictive drugs.
Prenatal meth exposure linked to abnormal brain development
A first of its kind study examining the effects of methamphetamine use during pregnancy has found the drug appears to cause abnormal brain development in children.
Methamphetamine use cost the US about $23 billion in 2005, RAND study estimates
The economic cost of methamphetamine use in the United States reached $23.4 billion in 2005, including the burden of addiction, premature death, drug treatment and many other aspects of the drug, according to a new RAND Corporation study.
Success of anti-meth ads questioned by study
An independent review investigating the effectiveness of a publicly funded graphic anti-methamphetamine advertising campaign has found that the campaign has been associated with many negative outcomes.
Methamphetamine abuse linked to underage sex, smoking and drinking
Teens who have never done drugs, but engage in other risky behaviours such as drinking, smoking and being sexually active, are more likely to use crystal meth, medical researchers at the University of Alberta have concluded.
Addiction treatment proves successful in animal weight loss study
Vigabatrin, a medication proposed as a potential treatment for drug addiction by scientists at the U.S. Department of Energy's (DOE) Brookhaven National Laboratory, also leads to rapid weight loss and reduced food intake according to a new animal study from the same research group.
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