cant. The observation of overt signs of toxicity, however, may necessitate a decision to terminate treatment earlier than expected. Daily observation of animals by someone familiar with the experimental protocol is especially important so that timely decision-making can occur.

Many dosing regimens do not produce long-term effects or behavioral impairment. After an appropriate washout time, the neuroscientist can determine the existence of long-lasting or irreversible effects (Bushnell et al., 1991). Irreversible effects do not pose a problem if the animal use-protocol calls for the animal to be euthanized to obtain cellular data to supplement functional results. A factor in the decision to euthanize is whether drug exposure has permanently altered a physiologic or behavioral function in such a way as to make providing adequate care for the animal difficult or to compromise continued humane use of the animal. But such an animal would be a valuable resource if the aim of the research is to understand mechanisms of tolerance, postexposure recovery, or therapeutic interventions that ameliorate long-lasting drug effects.


The previous section addressed a wide array of issues related to acute and chronic effects of various chemical agents, including drugs. This section extends that discussion by focusing on issues related to the testing of drugs that are of interest because their chronic use or exposure produces neuroadaptations thought to underlie the behavior patterns (such as tolerance and sensitization, dependence, and withdrawal) that characterize addiction to alcohol, nicotine, cocaine, heroin, and other abused drugs. Neuroscientists study the brain mechanisms that establish and maintain addiction in order to identify and characterize variables that affect risk (for example, genotype, environment, and experience) and to develop methods for treating addictive behavior and preventing relapse (e.g., Koob and Le Moal, 2001). Neuroscientists are also interested in characterizing the neurobiologic consequences of chronic exposure to addictive agents (such as changes in brain structure or function) (Becker, 1996; Obernier et al., 2002) and the process of recovery from deficits induced by such exposure.

General Considerations

Studies of addictive agents often require attention to dose, route of administration, vehicle, and other variables discussed in the previous section (see also NIH, 2002). When drugs are to be administered with abuse potential, the possibility that an animal will receive a harmful overdose must be carefully considered in the determination of the amount of each dose, the minimum interval between doses, and the total number of doses per session. Those factors depend on drug

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