commandeer circuits intimately involved in the control of emotion and motivation, thus impairing the insight and volitional control of the addicted person. At the same time, the alterations produced by chronic drug use facilitate the formation of deeply ingrained emotional memories that predispose to drug craving and hence to relapse.

Thus, in developing a conceptual understanding of addiction, it must be acknowledged that compulsive drug use cannot be understood from any single level of analysis. The development of drug addiction, at a minimum, involves the properties of the drugs involved, the neural circuits on which they operate,

BOX 3.1 Animal Models: Examples from Alcohol Research

Experimental laboratory animal models remain an essential resource in modern biomedical research because large segments of investigation require the intact animal. This is particularly true for behavioral disorders, including the addictive disorders, and self-administration models are particularly useful for studying all psychoactive substances in animals. Self-administration models, although they vary in specific aspects, all involve making the animals capable of administering drugs to themselves by performing some action, such as pressing a bar or entering a chamber.

Consistent self-administration of alcohol can be established in primates, rodents, and other animals. These techniques have contributed to better understanding of the behavioral and biological conditions of ethanol intake. In many aspects, these procedures mimic the "learning to drink" phenomenon evident in humans. These procedures are used to study the pharmacodynamic effects of ethanol, such as acute intoxication, tolerance, and dependence, and to study the medical consequences of chronic ingestion; for example, fetal alcohol syndrome (FAS), brain damage, and liver disease. Self-administration models are particularly useful in studying the behavioral patterns and consequences of ethanol ingestion.

The finding that food deprivation leads to increased ethanol intake in ethanol self-administration models provides a better understanding of the relationship between drug use and eating disorders. Alcohol is also commonly taken with other drugs and the self-administration model, where animals, like humans, take in substantial quantities of drugs and become dependent, also provides a means to examine the outcomes of multiple drug use. Further, animal self-administration models provide opportunities to examine the effects of potential medications for the treatment of alcohol dependence (e.g., naltrexone). Test medications are also evaluated to determine whether they sustain drug taking or might be abused. The strength of this model is such that the Food and Drug Administration (FDA) and Drug Enforcement Administration (DEA) rely heavily on self-administration evaluations to determine the "abuse liability" of drugs for purposes of scheduling under the Controlled Substances Act.



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