Anthony Dekker D.O., Director of Ambulatory Care and Community Health at Phoenix Indian Medical Center, replies:

A BRAIN ON BOOZE Image: MOUNT HOLYOKE COLLEGE UNDER THE INFLUENCE of alcohol, the brain experiences impairments in the regions shown: Frontal Lobe (A) Loss of reason, caution, inhibitions, sociability, talkativeness and intelligence Parietal Lobe (B) Loss of fine motor skills, slower reaction time, shaking Temporal Lobe (C) Slurred speech, impaired hearing Occipital Lobe (D) Blurred vision, poor distance judgement Cerebellum (E) Lack of muscle coordination and balance Brain Stem (F) Loss of vital functions

The product of the oldest chemical reaction studied by man<, alcohol, continues to challenge researchers. Since the original work on alcohol's neurological effects in the early 20th century, new theories have regularly emerged. What we have learned is that alcohol is a sedative-hypnotic in the acute intoxication phase for most patients. But it diminishes the quality of sleep. Individuals with sleep apnea often experience longer and more severe apneic episodes and hypoxia, or oxygen deprivation, after drinking alcohol.

In other individuals, though, alcohol may act as a stimulant. Indeed, its association with violent and self-abusive behavior is well documented. At intoxicating levels, alcohol is a vasodilator (it causes blood vessels to relax and widen), but at even higher levels, it becomes a vasoconstrictor, shrinking the vessels and increasing blood pressure, exacerbating such conditions as migraine headaches and frostbite. Researchers have also thoroughly documented the effects of alcohol on the developing fetus. Approximately one third of all babies born to alcoholic mothers will develop Fetal Alcohol Syndrome or Effects (FAS or FAE), causing central nervous system (CNS) dysfunctions including Attention Deficit Disorder (ADD) and impaired IQ. There are also growth and facial abnormalities associated with these infants.

In the early 1900s, H. Meyer and Charles Ernest Overton originally theorized that the effect of alcohol was achieved by altering the lipid environment of cell membranes. This theory, however, requires much higher concentrations of alcohol than are clinically observed. A recent theory, supported by several researchers, pins alcohol's effect on voltage and ligand-gated ion channels that control neuronal activity. Two distinct ligand-gated channels have been identified, inhibitory ones (GABA receptors and strychnine-sensitive glycine receptors) and excitatory ones (N-methyl-D-aspartate (NMDA) and non-NMDA glutamate-activated channels and the 5HT3 subtype of serotonin receptors).

The inhibitory aspect occurs due to a hyperpolarization of neurons, secondary to an influx of chloride ions. The neuron becomes less likely to achieve the threshold membrane potential. The excitatory receptor is dependent on the NMDA and non-NMDA glutamate receptors that control the influx of sodium and calcium, which bind to endogenous neurotransmitters (glutamate or aspartate) and depolarize the neuronal membrane. The NMDA receptor seems to have a high permiability to calcium, which acts as a catalyst to several intracellular events.

Chronic exposure to alcohol seems to alter the NMDA receptors and this may play a role in the clinical symptoms of alcohol withdrawal. In vitro studies have demonstrated an increase in the binding sites for MK801 (dizocilpine) in neurons chronically exposed to alcohol. This rise may account for the acclimation process, in which greater concentrations of alcohol are needed to cause experimental and clinical symptoms of intoxication. NMDA can cause seizure activity. Mice that have been exposed to chronically elevated levels of alcohol reveal increased numbers of NMDA receptors and NMDA related seizure activity. The NMDA antagonist MK801 has been shown to decrease the severity of seizures in these mice during withdrawal. Through a complex process of cell membrane ion pumps and neurotransmitter stimulation, the multi-faceted effects of alcohol and alcohol withdrawal are becoming better understood.

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