In humans, some of the neurotoxic effects associated with long-term alcohol abuse include anterograde and retrograde amnesia, dementia, ataxia, dysarthria, and peripheral-nerve disorders. Wernicke's syndrome and Korsakoffs syndrome are associated with chronic alcohol abuse primarily due to an alcohol-induced thiamine deficiency. Histologic features of these syndromes include microscopic lesions in the thalamus, hypothalamus, mesencephalon, and brainstem as well as cerebellar and cortical lesions (79-82).
The few studies of ethanol effects after inhalation exposure have indicated that, in humans, the initial symptoms of ethanol exposure are coughing, eye and nose irritation, which appear at a concentration of approximately 5,000- 10,000 ppm. At about 15,000 ppm, these symptoms increase, and continuous lachrymation and coughing occur. Concentrations of 20,000 ppm and above were judged as intolerable (83). In rodents, constant exposure to air concentrations of ethanol from 7,500 ppm to 15,000 ppm for 4-10 days produces signs of alcohol intoxication, dependency, and withdrawal. Pregnant rats exposed to air concentrations of ethanol at 16,000 ppm or 20,000 ppm exhibit signs of intoxication and reduced weight gain. Twenty-dayold fetuses of dams exposed at the 20,000 ppm concentration exhibited a significant increase in visceral and/or skeletal malformations. Rats exposed to 10,000 ppm showed no maternal or fetal effects (84-87).
The developmental deficits associated with fetal alcohol syndrome (FAS) and fetal alcohol effects (FAE), as well as "social drinking" during pregnancy, have been the topic of numerous publications. FAS and FAE infants display increased irritability, tremulousness, and reduced weight gain. Older children display increased social and emotional problems and intellectual impairment that may continue into adulthood. Offspring of social-drinking women display lower birthweights, abnormal state regulation, lower scores on infant developmental tests, growth retardation, increased restlessness, short attention span, and motor dysfunction. The pattern of alcohol consumption most related to the effects observed in offspring of social drinkers is more than two drinks/day during midpregnancy and binge drinking (more than five drinks/occasion) in the months just before pregnancy recognition (88-91). Several animal models have been developed to replicate the behavioral findings reported for humans (92). In addition, studies using animal models have investigated the neuroanatomical and neurochemical effects of prenatal alcohol exposure. Most of the studies concerning the neurochemical effects have focused on the GABAergic system (93,94). The results of these studies, however, have not provided a consistent pattern of effects. The inconsistency may be due to a biphasic dose-dependent response of GABA to ethanol. Results indicate that glutamine and GABA increase at low-level exposure (2 g/kg ethanol) but decrease at higher exposure concentrations (3 and 8 g/kg) (94). Not all studies on the neurochemical effects of alcohol have focused on the GABAergic system. Rats intubated with 4 g/kg ethanol every 12 hr for 11-15 days exhibited a significant reduction in the binding of mesolimbic dopamine receptors (20%). The binding of serotonin receptors was significantly increased in the striatum (63%) and brainstem (32%) and was significantly decreased in the hippocampus (20%). The binding of acetylcholine receptors was also significantly increased in the striatum (7%) and significantly decreased in the cerebral cortex (5%) (95). Finally, recent results from studies of nonhuman primate infants exposed to weekly doses of ethanol have provided some data regarding prenatal alcohol effects. Microphthalmia, retinal ganglion cell loss, and altered striatal dopamine concentrations have been reported thus far (96).
A summary of the neurotoxic effects reported for ethanol is shown in Table 7. Thus far, the most sensitive indexes of alcohol exposure effects are those observed after maternal alcohol intake during pregnancy. Offspring effects on behavior have been reported at blood alcohol concentrations associated with the intake of > 1 oz of absolute alcohol per day.
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