Contingent tolerance to amphetamine hypophagia: new insights into the role of environmental context in the expression of stereotypy.

A growing literature attests to the fact that the environment in which a drug is given can have a profound effect on the development and expression of tolerance and sensitization. The dominant paradigm for studying such context-dependency is based on Pavlovian conditioning, in which a distinctive environment serves as a conditioned stimulus. Context dependency is demonstrated when tolerance or sensitization is expressed only in the environment in which the drug was given chronically. An alternative paradigm for studying context-dependency is to manipulate the contingencies of reinforcement operating in the environment in which the drug is administered. For example, tolerance to amphetamine-induced hypophagia is contingent on having access to food while intoxicated [Carlton PL, Wolgin DL. Contingent tolerance to the anorexigenic effects of amphetamine. Physiol Behav 1971;7:221-223]. Such context-dependency can be explained in terms of an instrumental (or operant) conditioning model, in which food serves as a reinforcer for the learned suppression of stereotyped movements that interfere with ingestion. Research based on this model suggests that the expression of sensitized stereotyped responses is subject to an operant level of control.