Situational specificity of tolerance to decreased operant responding by cocaine.

Responding of rats was maintained in three different environmental situations each day. Interruption of a photobeam was maintained under a shock avoidance schedule in the first session, lever pressing was maintained under a 5-min fixed-interval (FI) schedule of food presentation in a second session, and nose-key pressing was maintained under a 30-response fixed-ratio (FR) schedule of food presentation in a third session. After receiving once-weekly injections of cocaine (3-17 mg/kg) prior to each of the sessions, animals received daily administration of 13 mg/kg after responding in the third daily session for four weeks, before responding in the third session for four weeks, before responding in the second daily session for four weeks, and then before responding in the first daily session for four weeks. Tolerance that developed in the environment that was coincident with the pharmacological actions of cocaine did not extend to operants in other environmental situations. Instead, tolerance to the behavioral effects of cocaine was specific to particular stimulus conditions associated with drug administration, indicating that the expression of tolerance depended on both pharmacologic action as well as concurrently operating behavioral processes.