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New study reveals brain cell mechanism of alcohol dependence
May 29, 2008Findings support new possible treatment for alcohol abuse
A study released today reveals a cellular mechanism involved in alcohol dependence. The study, in the May 28 issue of The Journal of Neuroscience, shows that gabapentin, a drug used to treat chronic pain and epilepsy, reduces alcohol intake in alcohol-dependent rats by normalizing chemical communication between neurons, which is altered by chronic alcohol abuse.
The central amygdala, a part of the brain involved in emotions such as stress and fear, is important in regulating alcohol consumption. Most central amygdala neurons communicate via a chemical signal known as GABA, which is an inhibitory neurotransmitter. Alcohol dependence has been associated with the strengthening of inhibitory synapses in this brain region.
Gabapentin (known commercially as Neurontin) is structurally similar to GABA and increases GABA neurotransmission. In alcoholics, gabapentin has been shown to effectively treat alcohol withdrawal and reduce alcohol consumption and cravings following detoxification. However, how gabapentin acts in the brain to combat alcohol dependence has been unclear.
The study's authors, led by Marisa Roberto, PhD, at the The Scripps Research Institute, made rats dependent on alcohol by chronically exposing them to ethanol in an aerosol or in their food. They then tested how much alcohol the rats voluntarily drank and examined neural signaling in the central amygdala.
The study authors found that gabapentin reduced alcohol intake in rats chronically exposed to alcohol, but not in rats that were chronically unexposed. Gabapentin reduced alcohol intake in alcohol-dependent rats whether it was given systemically or infused directly into the central amygdala, supporting the importance of the central amygdala in alcohol dependence.
"What I find to be important about this paper is that gabapentin's effect on alcohol consumption is only seen in alcohol-dependent rats," said Julie Blendy, PhD, at the University of Pennsylvania, an expert unaffiliated with the study. "For me, this speaks volumes to the addiction field, in that therapeutic targets for addiction-which have been few and far between-may be missed when examined in animal studies that use only minor exposures of alcohol," said Blendy.
Gabapentin corrected the cellular effects of chronic alcohol exposure. Both gabapentin and alcohol increase GABA neurotransmission in the central amygdala of non-alcohol-dependent rats, but in alcohol-dependent rats, gabapentin reduced it, suggesting that altered GABA neurotransmission is key to alcohol dependence.
In the study, gabapentin and chronic alcohol exposure both affected GABA B (GABAB) receptors. The authors believe that alcohol abuse alters the function of these receptors, and gabapentin may be able to counteract alcohol dependence by regulating their function.
"This study provides important mechanistic insights," said Robert Messing, MD, at the Ernest Gallo Clinic and Research Center at the University of California at San Francisco, an expert also uninvolved with the study. "Because gabapentin is well tolerated, this paper provides a strong rationale for large clinical trials testing whether gabapentin is an effective treatment for alcoholism in both detoxified and actively drinking alcoholics," Messing said.
Society for Neuroscience
Gabapentin (known commercially as Neurontin) is structurally similar to GABA and increases GABA neurotransmission. In alcoholics, gabapentin has been shown to effectively treat alcohol withdrawal and reduce alcohol consumption and cravings following detoxification. However, how gabapentin acts in the brain to combat alcohol dependence has been unclear.
The study's authors, led by Marisa Roberto, PhD, at the The Scripps Research Institute, made rats dependent on alcohol by chronically exposing them to ethanol in an aerosol or in their food. They then tested how much alcohol the rats voluntarily drank and examined neural signaling in the central amygdala.
The study authors found that gabapentin reduced alcohol intake in rats chronically exposed to alcohol, but not in rats that were chronically unexposed. Gabapentin reduced alcohol intake in alcohol-dependent rats whether it was given systemically or infused directly into the central amygdala, supporting the importance of the central amygdala in alcohol dependence.
"What I find to be important about this paper is that gabapentin's effect on alcohol consumption is only seen in alcohol-dependent rats," said Julie Blendy, PhD, at the University of Pennsylvania, an expert unaffiliated with the study. "For me, this speaks volumes to the addiction field, in that therapeutic targets for addiction-which have been few and far between-may be missed when examined in animal studies that use only minor exposures of alcohol," said Blendy.
Gabapentin corrected the cellular effects of chronic alcohol exposure. Both gabapentin and alcohol increase GABA neurotransmission in the central amygdala of non-alcohol-dependent rats, but in alcohol-dependent rats, gabapentin reduced it, suggesting that altered GABA neurotransmission is key to alcohol dependence.
In the study, gabapentin and chronic alcohol exposure both affected GABA B (GABAB) receptors. The authors believe that alcohol abuse alters the function of these receptors, and gabapentin may be able to counteract alcohol dependence by regulating their function.
"This study provides important mechanistic insights," said Robert Messing, MD, at the Ernest Gallo Clinic and Research Center at the University of California at San Francisco, an expert also uninvolved with the study. "Because gabapentin is well tolerated, this paper provides a strong rationale for large clinical trials testing whether gabapentin is an effective treatment for alcoholism in both detoxified and actively drinking alcoholics," Messing said.
Society for Neuroscience
Alcohol Dependence Current Events and Alcohol Dependence News RSSDrinking alcohol before 15 years of age is risky for later alcohol problems
It may seem like a minor point, but it matters when someone takes their first drink of alcohol relative to later development of alcohol problems. A new study of the relationship between age at first drink (AFD) and the risk of developing alcohol-use disorders (AUDs) during adulthood has found that the risk is greatest when AFD occurs before the age of 15.
Caffeine experts at Johns Hopkins call for warning labels for energy drinks
Johns Hopkins scientists who have spent decades researching the effects of caffeine report that a slew of caffeinated energy drinks now on the market should carry prominent labels that note caffeine doses and warn of potential health risks for consumers.
Alcohol dependence among women is linked to delayed childbearing
Alcohol use during the teen years can not only lead to subsequent alcohol problems, it can also lead to risky sexual behavior and a greater risk of early childbearing. An examination of the relationship between a lifetime history of alcohol dependence (AD) and timing of first childbirth across reproductive development has found that AD in women is associated with delayed reproduction.
Alcohol consumption declining, according to results of new study
Overall alcohol use-particularly consumption of beer-is declining in the US, according to a new study published in the August 2008 issue of The American Journal of Medicine.
Epilepsy drug may help alcoholics recover from dependence, small study suggests
It's a Catch-22 of the highest order. People with alcohol problems often use alcohol to get to sleep -- but it actually keeps them from getting good-quality sleep all night long.
Alcoholism-associated molecular adaptations in brain neurocognitive circuits
After many years of heavy drinking, alcohol produces pathological alterations in the brain. In many alcoholics these changes culminate in massive social deterioration and disorders of memory and learning.
Initiating drinking at younger age heightens women's risk for alcohol dependence
Women born after 1944 began drinking alcohol at younger ages than their elders, and that appears to have put them at greater risk for alcoholism, according to researchers at Washington University School of Medicine in St. Louis.
Study finds link between amphetamine abuse and heart attacks in young adults
Young adults who abuse amphetamines may be at greater risk of suffering a heart attack, UT Southwestern Medical Center researchers have found.
Report confirms increased risk of smoking, substance abuse in bipolar adolescents
A study from the Massachusetts General Hospital (MGH) supports previous reports that adolescents with bipolar disorder are at increased risk for smoking and substance abuse.
Drinking at an early age can lead to later alcohol dependence
An early age at onset of drinking (AOD) is a strong predictor of subsequent alcohol dependence (AD). Following through on previous research that found substantial increases in drinking and AD among women born between 1944 - 1983, compared to women born between 1934 - 1943, this study examined the influence of AOD.
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