Bioassay of subjective effects associated with benzodiazepine withdrawal in animals: A novel direction in dependence research

In humans, the earliest arising and most readily detectable symptoms of withdrawal from drugs of dependence are subjective in nature. For most substances with dependence liability, as withdrawal progresses, subjective symptoms are superseded by more vivid physical manifestations of abstinence, and it is only these latter phenomena that have been well characterized in the drug-dependence literature. Significantly, however, continuation of the self-administration cycle in man is not contingent on the emergence of overt behavioral signs of withdrawal; therefore, subjective events occurring early during drug withdrawal may be an important factor in continued drug dependence. By definition, subjective events are not directly verifiable by experimenter observation, and because of the dangers of anthropomorphism, animal investigations of subjective events are particularly difficult. This paper illustrates application of drug discrimination technology to quantify in animals a subjective factor that frequently occurs in man during withdrawal from drugs of dependence.