Researchers know that alcohol, in addition to facilitating gamma-aminobutyric acid (GABA) activity, also affects other neurotransmitter systems in the brain. It is likewise clear that alcohol, which has both sedative-like and stimulant-like effects, has addictive qualities. Benzodiazepines (used as sleeping pills) - which primarily facilitate GABAergic activity in the brain - have mainly sedative effects, but are also addictive. In order to differentiate amongst the brain circuits involved in the sedative versus the stimulant properties of alcohol, a study published in the June issue of Alcoholism: Clinical & Experimental Research compares alcohol’s effects on the brain with those of a benzodiazepine drug called lorazepam (commercially known as Ativan).
"We wanted to investigate which areas of the brain were responsible for the stimulant - versus the sedative - effects of alcohol because these two effects appear to contribute to the abuse of alcohol in different subject populations," said Nora D. Volkow, associate laboratory director of Life Sciences, Brookhaven National Laboratory at the U.S. Department of Energy and senior author of the study. "In general, alcohol’s stimulant effects are associated with its reinforcing effects, whereas its sedative effects interfere with its abuse; yet the sedative effects of alcohol are desirable in anxious individuals."
"People often think of alcohol as having a depressant effect," explained Gene-Jack Wang, chairman of the Medical Department, Brookhaven National Laboratory at the U.S. Department of Energy and first author of the study, "but alcohol actually has a dual effect. In general, most people initially feel euphoric and stimulated after drinking alcohol, but later feel sleepy and sedated. The sedative effect is similar to that of Ativan, a sleeping pill. We wanted to compare the activity of the brain during alcohol intoxication with that seen after administration of a sedative drug. For this purpose, we used positron emission tomography (PET), an imaging method that allowed us to measure the consumption of sugar by the different regions of the brain, which served as an indicator of their level of activity." Wang added that since PET imaging was developed in the late 1970s, it has been used for cancer, heart and brain (including alcohol) research.
The study used PET technology to scan and compare the effects of a moderately high dose of alcohol (equivalent to three glasses of wine) with the effects of the benzodiazepine drug Ativan, which had been investigated in an earlier study. In both studies, the subjects were healthy, ‘normal’ males. In other words, none was an alcoholic.
"This study uses a unique technology - namely, PET scans - that allows us to look at the effects of alcohol on brain function while the person is awake," said Harriet de Wit, associate professor in the Department of Psychiatry at the University of Chicago. "Different researchers have been looking at the effects of drugs on brain activity using this technology, and this study uses it to look at alcohol. In addition, it compares the findings from this study with those from an earlier study on a drug which has a known effect on one neurotransmitter."
"We found that both drugs induced marked reductions in whole brain activity," said Volkow. "The reductions were most accentuated in the occipital cortex (visual area) and in the cerebellum (an area involved with motor control), which we believe is due to the fact that these areas have a very high concentration of GABA receptors." However, there were significant differences in brain activity changes induced by these two drugs, she noted.
"Ativan produced significantly larger reductions in activity in the thalamus (a brain region involved with sleep regulation) than alcohol did," Volkow said. "We believe that this difference accounts for the fact that Ativan was more sedating than alcohol. Moreover, after Ativan, the reduction in thalamic activity was associated with more intense self-reports of ‘sedation’ and ‘sleepiness.’ The larger decrements in thalamic activity associated with Ativan likely reflect the fact that there are differences in sensitivity between the different types of GABA receptors to the effects of alcohol than to those of benzodiazepines. Alternatively," she added, "this could reflect the effects of alcohol on other neurotransmitters that antagonize the decrements in thalamic activity."
Alcohol induced larger decrements in the basal ganglia, which is a brain region that receives extensive innervation (supply) from dopamine, a neurotransmitter implicated in the reinforcing effects of drugs of abuse, including those of alcohol. Alcohol was perceived as more stimulating and more reinforcing than Ativan, as assessed by self-reports of ‘stimulated,’ ‘high’ and ‘drug liking.’
"We know that alcohol’s effects on the brain go beyond its effects on GABA receptors," said Wang. "Alcohol is a ‘dirty drug’ in that it acts on many brain systems, including dopamine. The larger changes in the basal ganglia caused by alcohol than by Ativan could reflect the effects of alcohol on dopamine, which in turn could account for it being perceived as more reinforcing and stimulating than Ativan."
"This study looks at a basic science question," said de Wit, " how does alcohol act on the brain? Alcohol seems to have different effects, both sedative-like and stimulant-like, on the brain. Healthy volunteers who experience the sedative-like effects usually don’t really like the drug; they tend to not be so much associated with drug seeking. People who experience the stimulant effects of alcohol like it more."
"However, there are certain individuals who are vulnerable to the sedative effects of alcohol as well as that of benzodiazepines," added Volkow. "These individuals may be abusing alcohol or benzodiazepines as a means to automedicate an anxiety disorder. In addition, one could speculate that chronic alcohol administration could result in decreases in brain GABA activity that could make an individual vulnerable to the sedative effects of alcohol."
Funding for this Addiction Science Made Easy project is provided by the Addiction Technology Transfer Center National Office, under the cooperative agreement from the Center for Substance Abuse Treatment of SAMHSA.
Articles were written based on the following published research:
Wang, G.J., Volkow, N.D., Franceschi, D., Fowler, J.S., Thanos, P.K., Scherbaum, N., Pappas, N., Wong, C.T., Hitzemann, R.J., & Felder, C.A. (2000, June). Regional brain metabolism during alcohol intoxication. Alcoholism: Clinical and Experimental Research, 24(6), 822-829.
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