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Last Updated: Tuesday, 4 January, 2005, 00:00 GMT
Block on effect of alcohol abuse
Alcohol triggers brain changes
Scientists believe they have identified the way alcohol abuse triggers changes to the brain that lead to dependence.

They believe long-term heavy drinking stimulates production of a protein which alters the way key brain receptors work.

The Rockefeller University researchers say it might eventually be possible to block the reaction, and reduce the risk of physical dependence.

Details are published in Proceedings of the National Academy of Sciences.

It is known that a protein called tissue plasminogen activator (tPA) interacts with receptors in the brain that play a key role in the learning process.

In experiments on mice, the Rockefeller team found that production of tPA was increased by long-term administration of - and withdrawal from - alcohol.

They believe the interaction between tPA and the receptors probably leads to physical alcohol dependence.

They are also confident that the same interaction is responsible for the physical symptoms - such as seizures, hallucinations and tremors - caused by alcohol withdrawal.

The research suggests that tPA increases the activity of a key part of the receptors, and that over time the body gets used to this state of heightened excitability.

Then, when alcohol is suddenly withdrawn, the over-stimulation of the receptors can trigger the symptoms of withdrawal.

Other factors

Writing in the journal, the researchers, lead by Dr Sidney Strickland, stress that the interaction between tPA and the receptors is not solely responsible for the development of physical dependence on alcohol, which is known technically as ethanol.

They add: "The action of ethanol in the brain is complex, and multiple neurotransmitters and receptors participate in the development of physical dependence to ethanol."

However, they go on to say: "These findings identify a tPA-dependent pathway of neuronal activation as a potential drug target against ethanol-related brain pathologies."

Researcher Dr Robert Pawlak told the BBC News website: "Alcohol addiction can be viewed as an abnormal form of brain adaptation.

"It is important to differentiate psychological dependence (cravings for alcohol) from physical dependence (withdrawal signs after termination of drinking).

"We do not know if tPA plays any role in psychological dependence and experiments are underway to clarify that."

Long-term alcohol abuse causes serious damage to brain, killing off brain cells, and leading to tissue shrinkage in key areas such as the cortex and cerebellum.

A spokeswoman for the charity Alcohol Concern said: "We would welcome any research that gives an insight into the basis of alcohol dependancy."

However, she said other studies would be needed to be able to draw firm conclusions.

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