seizure). In cases in which feeding and drinking decline to some predetermined level, it is 
important to have a contingency plan for alternative feeding. Withdrawal is, by definition, a 
time-limited phenomenon, and thus true withdrawal signs revert toward a pre-drug baseline 
level over time after drug withdrawal. If the withdrawal syndrome is not a subject of study, 
dose-tapering regimens or substitution of other drugs to ameliorate withdrawal can be 
implemented for drugs for which it is known that the withdrawal syndrome can be severe 
after prolonged administration (e.g., opioids, barbiturates), just as they would be with 
humans. In cases in which the withdrawal syndrome is very brief and/or mild, however, dose 
tapering is not necessary. 
DURATION OF DRUG OR TOXICANT EXPOSURE 
In experiments involving study of the direct effects of chronic exposure (e.g., possible 
deterioration of performance under repeated exposure to a neurotoxin or the development of 
tolerance to an initial effect of a drug), two questions require particular attention: the length 
of drug exposure and the disposition of the animal. The decision to end chronic drug 
exposure typically is based on predetermined criteria that establish a range of changes from 
baseline behavior that will be considered significant. Termination of exposure may also be 
planned to obtain tissue specimens. The observation of overt signs of toxicity, however, may 
necessitate a decision to terminate treatment earlier than anticipated. Daily observation of 
animals by someone familiar with the experimental protocol is especially important in studies 
involving chronic drug or toxicant administration so that timely decision-making can occur. 
LONG-LASTING DRUG EFFECTS 
The dosing regimens used in many behavioral studies do not produce long-term effects or 
behavioral impairment. After an appropriate wash-out time, the researcher can determine the 
existence of long-lasting or irreversible effects (Bushnell et al., 1991). Irreversible effects are 
not a problem if the protocol calls for the animal to be sacrificed to obtain cellular data to 
supplement the behavioral results. Another factor in the decision to sacrifice is when it is 
believed that chronic drug exposure altered a physiological or behavioral function that 
compromises the animal for use in future studies. On the other hand, such an animal would 
be a valuable resource when the aim of the research is to understand mechanisms of 
tolerance, post-exposure recovery, or therapeutic interventions that ameliorate long-lasting 
drug effects. ■ 
REFERENCES 
Ator, N.A. (1991). Subjects and instrumentation. In I.H. Iversen and K.A. Lattal (Eds.), 
Techniques in the behavioral and neurological sciences (Vol. 6): Experimental analysis of 
behavior, Part 1 (pp. 1-62). Amsterdam: Elsevier. 
Barrett, J.E. (1991). Behavioral neurochemistry. In l.H. Iversen and K.A. Lattal (Eds.), 
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