Episodes of heavy alcohol consumption leading to intoxication are associated with many health and safety problems, including unintentional injuries, sexual assault, domestic violence and alcohol poisoning. Previous studies have shown that brain molecules called GABAA receptors appear to play a role in excessive drinking. In a new study, researchers used an established rat model of binge drinking to investigate how GABAA receptors interact with other brain molecules to influence excessive drinking. The researchers established, for the first time, a direct connection between a molecule known as Toll-like receptor 4 (TLR4) and GABAA receptors. TLR4 is an innate immune system molecule that contributes to the inflammation and brain damage brought on by excessive drinking. Using gene therapy techniques, the researchers targeted TLR4 and GABAA receptors in brains of heavy-drinking rats. They found that silencing the genes for TLR4 and GABAA receptors in certain areas of the brain caused the rats to lose interest in alcohol, an effect that lasted for two weeks after the procedure. The new findings provide exciting new knowledge about the biology of binge drinking in this animal model. It is an important step in understanding brain pathways involved in excessive alcohol consumption and reveals new targets for exploring therapeutic interventions for human drinking.
Alcohol use during pregnancy contributes to many problems in exposed children. Heavy prenatal alcohol exposure leads to fetal alcohol syndrome, a devastating birth defect characterized by craniofacial malformations, neurological and motor deficits, intrauterine growth retardation, learning disabilities, and behavioral and social deficits. Most women who drink alcohol during pregnancy, however, are light-to-moderate drinkers in early pregnancy and quit or decrease their alcohol use by mid-pregnancy. In this long-term study, researchers examined effects of lower levels of prenatal alcohol exposure. They specifically focused on the relation of prenatal alcohol exposure to a subsequent diagnosis of conduct disorder during childhood. Conduct disorder is a pattern of aggressive, destructive, or unlawful behavior problems. The study sample included 592 adolescents and their mothers. Women in the study were interviewed at their fourth and seventh prenatal months, and then at routine intervals post-partum until their children were 16 years old. The researchers found that children who had been exposed to an average of one or more drinks of alcohol per day in the first trimester of pregnancy were three times more likely to meet criteria for a diagnosis of conduct disorder than were adolescents whose mothers drank less than that amount or abstained.
Some people experience the initial effects of alcohol as stimulating and euphoric, while others experience mostly unpleasant sedative effects. How individuals’ immediate responses to alcohol influence their future drinking behavior has been an active area of scientific research. One theory holds that people who have a low level of positive response to alcohol and who also are less sensitive to internal cues and warning signs to stop drinking, are more likely to drink to excess and develop alcohol problems. However, this low-level response theory has been contradicted by studies which suggest that people who drink heavily experience greater alcohol-induced positive effects. To help resolve these issues, scientists investigated the acute effects of alcohol among nearly 200 young adults who were divided into groups of heavy and light drinkers based on their drinking histories. In three separate testing sessions, the subjects received one of three drinks: a placebo, a low dose of alcohol, or a high dose of alcohol. A flavoured drink mix made all of the concoctions taste the same, so none of the subjects knew what they were drinking. For the next three hours, the subjects took breath alcohol tests and answered questions that allowed the researchers to measure a variety of positive and negative effects. The scientists found that alcohol produced greater stimulant and rewarding responses and lower sedative responses among the heavy drinkers than the light drinkers. Over a 2-year follow-up period, greater positive effects and lower sedative effects after alcohol consumption predicted increased binge drinking frequency. In turn, greater frequency of binge drinking during follow-up was associated with greater likelihood of meeting diagnostic criteria for alcohol abuse and dependence. The new data could help clinicians identify and prevent unhealthy drinking habits.
Recent research suggests that receptors for the neurotransmitter GABA(A) that lie outside of the synapse and which contain a molecular fragment known as a delta-subunit are sensitive to alcohol, raising the possibility that these receptors might help produce alcohol’s reinforcing effects after consuming one or a few drinks. In the current study, researchers tested the hypothesis that these extrasynaptic GABA(A) receptors in an area of the brain’s reward circuitry called the nucleus accumbens (NAc) are necessary for oral alcohol consumption. They used genetic-engineering technology to reduce expression of the GABA(A) receptor delta-subunit in adult rats in different parts of the NAc, a structure that consists of a core and a shell, which is subdivided into ventral, medial, and dorsal parts. They found that by inhibiting the delta-subunit in the medial shell region of the NAc, but not in the ventral or lateral shell or in the core, reduced the rats’ alcohol intake. In contrast, delta-subunit inhibition in the medial shell did not affect intake of a 2% sucrose solution, suggesting that the effects of GABA(A) receptor delta-subunit reduction are specific to alcohol. The findings provide strong evidence that extrasynaptic delta-subunit-containing GABA(A) receptors in the medial shell of the NAc are critical for the reinforcing effects of oral ethanol.
Alcohol consumption and its harms are common among young people, including those who are below the legal drinking age of 21. Some people argue that the current age-21 drinking limit in the United States is “not working,” and propose that the drinking age be lowered to 18. Researchers recently conducted economic analyses to estimate the effects of the minimum legal drinking age (MLDA) on deaths, injuries, crime, and alcohol consumption, and to identify the costs and benefits of lowering the drinking age to 18. They report that a large body of evidence shows that setting the MLDA at 21 clearly reduces alcohol consumption and its major harms. They estimate that lowering the MLDA to 18 would result in an additional 8 deaths per 100,000 person years for the 18–20 age group. Using a common estimate of the value of a statistical life of $8.72 million, this suggests that for every 100,000 young adults allowed to drink legally for a year the cost in terms of increased mortality is about $70 million. The researchers also estimate that lowering the drinking age would impose additional costs on others for crime, health care, and deaths of non-drinking drivers and passengers of at least $12 million annually for every 100,000 newly legal drinkers. These estimates suggest that each extra drink consumed as a result of lowering the MLDA would generate harms valued at more than $15 to the drinker plus at least an additional $2.63 in harms imposed on others, all in addition to the purchase price of the drink. The researchers conclude that “…the evidence strongly suggests that setting the minimum legal drinking age at 21 is better from a cost and benefit perspective than setting it at 18 and that any proposal to reduce the drinking age should face a very high burden of proof.”