trained to respond differently to the test drugs (e.g., drug versus placebo or drug versus drug). For example, a research subject might be trained to press the left lever after a dose of amphetamine and the right lever after a dose of placebo. After training, research subjects (nonhuman or human) will respond differentially to drug and placebo, allowing for comparison among drugs and for conclusions about pharmacological and behavioral similarity, depending on the manner in which the trained research subject responds.
Drug dependence has also been modeled in laboratory animals. Drug dependence (or addiction), as noted in Chapter 1, is characterized in both the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; APA, 1994) and the International Classification of Diseases (ICD-10, WHO, 1992) as drug-seeking behavior involving compulsive use of high doses of one or more drugs, for no clear medical indication. Dependence is usually accompanied by tolerance and withdrawal; physicians often confuse the presence of a withdrawal syndrome (i.e., physical dependence) with the compulsive drug taking that is a part of the behavioral dependence syndrome. Models have been developed in which animals are maintained on specific drugs of abuse (e.g., opiates) for some period of time, either via self-administered or experimenter-administered drug, and then observed for the effects of abrupt cessation (e.g., Woods and Schuster, 1968). Manipulations using animal models have provided information about the relationship between repeated drug use and toxicity, as well as the likelihood that the drug will be taken in the future.
In addition to being a useful tool for investigating basic biobehavioral mechanisms underlying drug abuse, the drug self-administration model has provided the foundation for research in many other areas of drug abuse. For example, it has been shown that there is a significant positive correlation between the potencies of cocaine (and other stimulants) as dopamine reuptake blockers and their ability to maintain self-administration behavior, although the same is not true for norepinephrine and serotonin (Ritz et al., 1987; Bergman et al., 1989). This finding suggests that the action of cocaine at its binding site, which results in dopamine uptake blockade, mediates the effects that contribute to abuse (Fischman and Johanson, 1996).