AsianScientist (Oct. 31, 2011) – Users of heroin and other addictive opioids may be spared from distressing withdrawal symptoms in the future, thanks to a research breakthrough by University of Sydney scientists.
In an article published yesterday in Nature Neuroscience, the researchers describe for the first time a protein in nerve cells that drives the withdrawal response – a complex and intensely unpleasant syndrome that includes chills, sweating, cramps, elevated heart rate and blood pressure, and increased sensitivity to pain.
“We have identified a protein in nerve cells that is driving the withdrawal response,” said senior author Prof. MacDonald Christie of the University of Sydney.
“When we either remove that protein from the brain or block it with experimental medications, then we can block withdrawal response and the aberrant activity of the nerves responsible for the painful withdrawal.”
Called GABA transporter 1 (GAT-1), the protein identified by researchers was found to produce excessive electrical activity in the brain during withdrawal from opioids.
“The electrical activity of the protein becomes excessive in the withdrawal phase. This stimulates the nerves to behave aberrantly and causes withdrawal symptoms,” said the article’s lead author Dr. Elena Bagley, a senior lecturer in pharmacology and researcher at the Brain & Medical Research Institute.
“This increased nerve excitability triggers the cascade of event that drives the opioid withdrawal syndrome. These highly excited nerve cells release more GABA, the neurotransmitter associated with the protein GABA transporter, and this GABA release decreases the chemical messages sent to other brain regions. The downstream dampening of signals to key brain regions such as the hypothalamus produces many of the withdrawal symptoms,” she explained.
The finding also explains for the first time why certain medications currently used to treat withdrawal symptoms work.
Although the finding was made using mice and rat models, the researchers are confident the discovery will lead to the development of new medications that can be used for humans, and also for other addictive substances such as cocaine and nicotine.
The article can be found at: Bagley EE et al. (2011) Drug-induced GABA transporter currents enhance GABA release to induce opioid withdrawal behaviors.
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Source: University of Sydney.
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