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Gene therapy reduces cocaine use in rats
April 16, 2008Flooding brain with 'pleasure chemical' receptors works on cocaine, as on alcohol
UPTON, NY - Researchers at the U.S. Department of Energy's Brookhaven National Laboratory have shown that increasing the brain level of receptors for dopamine, a pleasure-related chemical, can reduce use of cocaine by 75 percent in rats trained to self-administer it. Earlier research by this team had similar findings for alcohol intake. Treatments that increase levels of these chemicals - dopamine D2 receptors -- may prove useful in treating addiction, according to the authors. The study will be published online April 16 and will appear in the July 2008 issue of Synapse.
"By increasing dopamine D2 receptor levels, we saw a dramatic drop in these rats' interest in cocaine," said lead author Panayotis (Peter) Thanos, a neuroscientist with Brookhaven Lab and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) Laboratory of Neuroimaging. "This provides new evidence that low levels of dopamine D2 receptors may play an important role in not just alcoholism but in cocaine abuse as well. It also shows a potential direction for addiction therapies."
The D2 receptor receives signals in the brain triggered by dopamine, a neurotransmitter needed to experience feelings of pleasure and reward. Without receptors for dopamine, these signals get "jammed" and the pleasure response is blunted. Previous studies at Brookhaven Lab have shown that chronic abuse of alcohol and other addictive drugs increases the brain's production of dopamine. Over time, however, these drugs deplete the brain's D2 receptors and rewire the brain so that normal pleasurable activities that stimulate these pathways no longer do - leaving the addictive drug as the only way to achieve this stimulation.
The current study suggests that cocaine-dependent individuals may have their need for cocaine decreased if their D2 levels are boosted. Thanos' lab previously demonstrated dramatic reductions in alcohol use in alcohol-preferring rats infused with dopamine D2 receptors (see: http://www.bnl.gov/discover/Winter_06/alcohol_1.asp). Thanos hypothesized that the same would hold true with other addictive drugs.
The researchers tested this hypothesis by injecting a virus that had been rendered harmless and altered to carry the D2 receptor gene directly into the brains of experimental rats that were trained to self-administer cocaine -- the same technique used in the earlier alcohol study. The virus acted as a mechanism to deliver the gene to the nucleus accumbens, the brain's pleasure center, enabling the cells in this brain region to make receptor proteins themselves.
The scientists examined how the injected genes affected the rats' cocaine-using behavior after they had been taking cocaine for two weeks. After receiving the D2 receptor treatment, the rats showed a 75 percent decrease in self-administration of the drug. This effect lasted six days before their cocaine self-administration returned to previous levels.
"This adds another piece to the puzzle of the complex role of dopamine D2 receptors in addiction," said Thanos.
DOE/Brookhaven National Laboratory
The D2 receptor receives signals in the brain triggered by dopamine, a neurotransmitter needed to experience feelings of pleasure and reward. Without receptors for dopamine, these signals get "jammed" and the pleasure response is blunted. Previous studies at Brookhaven Lab have shown that chronic abuse of alcohol and other addictive drugs increases the brain's production of dopamine. Over time, however, these drugs deplete the brain's D2 receptors and rewire the brain so that normal pleasurable activities that stimulate these pathways no longer do - leaving the addictive drug as the only way to achieve this stimulation.
The current study suggests that cocaine-dependent individuals may have their need for cocaine decreased if their D2 levels are boosted. Thanos' lab previously demonstrated dramatic reductions in alcohol use in alcohol-preferring rats infused with dopamine D2 receptors (see: http://www.bnl.gov/discover/Winter_06/alcohol_1.asp). Thanos hypothesized that the same would hold true with other addictive drugs.
The researchers tested this hypothesis by injecting a virus that had been rendered harmless and altered to carry the D2 receptor gene directly into the brains of experimental rats that were trained to self-administer cocaine -- the same technique used in the earlier alcohol study. The virus acted as a mechanism to deliver the gene to the nucleus accumbens, the brain's pleasure center, enabling the cells in this brain region to make receptor proteins themselves.
The scientists examined how the injected genes affected the rats' cocaine-using behavior after they had been taking cocaine for two weeks. After receiving the D2 receptor treatment, the rats showed a 75 percent decrease in self-administration of the drug. This effect lasted six days before their cocaine self-administration returned to previous levels.
"This adds another piece to the puzzle of the complex role of dopamine D2 receptors in addiction," said Thanos.
DOE/Brookhaven National Laboratory
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ISU researchers' findings bring hope for possible Parkinson's disease cure
Researchers at Iowa State University have found an essential key to possibly cure Parkinson's disease and are looking for others.
Widely used cholesterol-lowering drug may prevent progression
Simvastatin, a commonly used, cholesterol-lowering drug, may prevent Parkinson's disease from progressing further. Neurological researchers at Rush University Medical Center conducted a study examining the use of the FDA-approved medication in mice with Parkinson's disease and found that the drug successfully reverses the biochemical, cellular and anatomical changes caused by the disease.
Stress-induced changes in brain circuitry linked to cocaine relapse
Stress-evoked changes in circuits that regulate serotonin in certain parts of the brain can precipitate a low mood and a relapse in cocaine-seeking, based on mouse studies published online this week in the Proceedings of the National Academy of Sciences.
Researchers find brain cell transplants help repair neural damage
A Swiss research team has found that using an animal's own brain cells (autologous transplant) to replace degenerated neurons in select brain areas of donor primates with simulated but asymptomatic Parkinson's disease and previously in a motor cortex lesion model, provides a degree of brain protection and may be useful in repairing brain lesions and restoring function.
Changes in brain chemicals mark shifts in infant learning
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Why antidepressants don't work for so many
More than half the people who take antidepressants for depression never get relief.
Cocaine exposure during pregnancy leads to impulsivity in male, not female, monkeys
Adult male monkeys exposed to cocaine while in the womb have poor impulse control and may be more vulnerable to drug abuse than female monkeys, even a decade or more after the exposure, according to a new study by researchers at Wake Forest University School of Medicine. The findings could lead to a better understanding of human drug abuse.
Scientists demonstrate link between genetic defect and brain changes in schizophrenia
Researchers at the University of North Carolina at Chapel Hill School of Medicine have found that the 22q11 gene deletion - a mutation that confers the highest known genetic risk for schizophrenia - is associated with changes in the development of the brain that ultimately affect how its circuit elements are assembled.
Fine-tuning treatments for depression
New research clarifies how neurotransmitters like norepinephrine, serotonin, and dopamine, are regulated - a finding that may help fine-tune therapies for depression.
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