Visualizing Neural Pathways Affected by Alcohol in Animals.

Alcohol has many short- and long-term effects on functional units of nerve cells, or neural pathways, in the brain. Imaging studies in laboratory animals, particularly studies using autoradiographic detection methods, allow researchers to analyze the activities of these pathways as well as alcohol's effects on them. Commonly used techniques measure blood flow, glucose utilization, protein synthesis, and the activity of the enzyme cytochrome oxidase throughout the animal's brain. Using these approaches, researchers have investigated alcohol's effects both in animals that receive alcohol for the first time and in animals with a history of alcohol exposure. These studies demonstrate that different alcohol doses affect different neural pathways and that the affected brain areas also vary depending on the time that has elapsed since alcohol ingestion. Moreover, chronic alcohol use can markedly alter the baseline activity of certain neural pathways, even in animals that are not alcohol dependent. KEY WORDS: neuron; animal model; AODE (alcohol and other drug effects); blood circulation; protein synthesis; enzymes; dose response relationship; glucose; radionuclide imaging; positron emission tomography; magnetic resonance imaging Alcohol is a pharmacologically complex agent that acts throughout the body via several different biological mechanisms (Nutt and Peters 1994). The overall effect depends on the amount of alcohol consumed, the time elapsed following ingestion, the rates of absorption and elimination (i.e., how fast the alcohol is absorbed into both the blood and the brain, and how fast the alcohol is metabolized in the body), and the response of particular tissues. In turn, metabolism and tissue response are influenced by certain characteristics of the drinker, such as age, gender, body weight, nutritional and general health status, and drinking history. Alcohol's effects on the brain also may be influenced by a person's lifestyle, the social context of alcohol consumption, and various psychological variables. Studies have shown, for example, that social drinkers consume more alcohol and report increased pleasure when they drink with others than when they drink alone (Doty and de Wit 1995). This multitude of factors, some of which cannot be easily controlled in clinical studies, makes it difficult to assess alcohol's effects on the human brain. Therefore, many researchers use laboratory animals as models to study alcohol's effects, because animal studies allow scientists to control their subjects' histories and genetic backgrounds as well as the environmental conditions under which the experiments take place. Unlike other organs, the brain comprises a myriad of anatomical components, each possessing a different level of organization and function. This complex organization is accomplished by linking together cells from different brain areas into functional units called neural pathways, or neuroanatomical circuits. The existence of these circuits implies that only a subset of brain cells, or neurons, needs to respond to any given stimulus. For example, an animal's first exposure to alcohol may alter the activity of particular pathways. After several weeks of alcohol exposure, a different set of pathways may be affected, owing to the animal's developed tolerance to the alcohol stimulus and to the corresponding physiological changes in the neurons. Researchers are attempting to identify the neural pathways affected by alcohol and to quantify the alcohol-induced changes in the living organism. A better understanding of the initial and residual effects of alcohol in the brain will help to better explain the causes of performance deficits in alcoholics and possibly aid in the development of new treatment approaches. Alcohol is only one of several commonly abused drugs. Other drugs, such as cocaine and heroin, also produce dramatic changes in brain activity. An important question addressed by alcohol studies in animals is whether all abused drugs affect a common neural pathway, sometimes referred to as the brain "reward system. …