Drug-induced state-dependent learning: review of an operant procedure in rats.

Drug discrimination and drug state dependence are often thought to be based on the same drug actions, and to differ only in the doses needed to produce them, with discrimination occurring at low doses and state dependence at high doses. Testing this hypothesis has been hampered by the use of discrimination and state dependence procedures that differed in many respects. In 1986, Colpaert introduced a procedure to study state dependence in rats that used the same response, the same reinforcer, and the same reinforcement schedule that are commonly used in drug discrimination. Using this procedure, differences between drug state dependence and drug discrimination were found with some drugs (e.g. alcohol), consistent with the hypothesis that the procedures differ in the drug properties they measure, but not with other drugs (e.g. chlordiazepoxide). Thus, state dependence and drug discrimination can generate different outcomes, but the conditions in which they do require further study. However, all the studies conducted with the procedure introduced by Colpaert clearly show that state dependence is not necessarily only a high-dose phenomenon, but can also occur at doses at which many central nervous system drugs produce their characteristic effects. This finding led to the hypothesis that state dependence may be involved in the therapeutic and other effects of psychoactive drugs.