Neurotransmitters Are Key to Treating Alcoholics

Doctor and nurse working with MRI brain scans seen through interactive display

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Scientist have been trying for many years to determine exactly how alcohol affects the brain in hopes of developing medications that will help people who are trying to quit drinking.

If we learn what chemical changes take place in the brain as a result of consuming alcohol, then the theory is, we can develop antagonists that will block the effects of alcohol, making it no longer pleasurable to drink.

Some researchers believe they have found a cellular mechanism underlying alcohol's behavioral and motivational effects and, when blocked, can stop alcohol's effect on the brain.

The Pleasure Centers of the Brain

The focus of this research has been on the amygdala, part of the circuitry in the pleasure centers of the brain. For years, researchers have known that alcohol produces much of its intoxicating action by facilitating one particular neurotransmitter called gamma-aminobutyric acid (GABA).

GABA is the brain's main inhibitory neurotransmitter and is widely distributed in the brain. Neurons use GABA to fine-tune signaling throughout the nervous system.

Several studies of alcohol use disorders have shown that GABA activity decreases in the pleasure center of the brain during alcohol withdrawal and during a protracted period of abstinence after the person quits drinking — that period of time when an alcoholic is particularly vulnerable to relapse.

Researchers believe that the changes in GABA activity in the amygdala during the initial post-acute withdrawal period are a major cause of relapse in people who are being treated for alcoholism.

CRF Peptide Linked to Alcohol Dependence

In trying to identify exactly how alcohol affects GABA receptor function, scientists at The Scripps Research Institute discovered that when neurons are exposed to alcohol they release a brain peptide known as corticotropin-releasing factor (CRF). A peptide is a short chain of amino acids.

CRF is a very common peptide in the brain that is known for activating in the amygdala sympathetic and behavioral responses to stressors. It has long been linked to the brain's response to stress, anxiety, and depression. CRF levels increase in the brain when alcohol is consumed.

The Effect of Alcohol Can Be Blocked

However, studies have found that CRF levels also increase when animals withdraw from alcohol, which could explain why alcoholics are vulnerable to relapse when they try to remain abstinent for a protracted amount of time.

Animal studies have found that when the CRF receptor is removed by genetic knockout, the effect of alcohol and CRF on GABA neurotransmission is lost.

In the Scripps study, Neuropharmacology Professor George Siggins and colleagues found that when they applied an antagonist of CRF, alcohol no longer had an effect.

"Not only did the antagonists block the effect of CRF in enhancing GABA transmission, but it also blocked the effect of alcohol," says Siggins. "The response was totally gone — alcohol no longer did anything."

Another Receptor Involved?

Siggins believes that developing a medication that blocks the effects of CRF, and therefore alcohol, on the pleasure centers of the brain, could help alcoholics who are trying to quit drinking avoid relapse.

However, a later study at the V.A. Medical Center in Durham, North Carolina found that CRF and the kappa-opioid receptor (KOR) are both implicated in stress-related behaviors and drug dependence.

The North Carolina researchers suggested that any potential medications targeted at behavioral and addictive disorders may need to involve both the CRF and KOR systems.

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Additional Reading
  • Siggins, GR, et al. "Ethanol Augments GABAergic Transmission in the Central Amygdala via CRF1 Receptors." Science March 5, 2004