RELATIONS BETWEEN DOSE MAGNITUDE, SUBJECT SENSITIVITY, AND THE DEVELOPMENT OF TOLERANCE TO COCAINE-INDUCED BEHAVIORAL DISRUPTIONS IN PIGEONS

Keypecking by 12 pigeons, maintained by a fixed-ratio 30 schedule of f ood presentation, was decreased in rate by acute pre-session injection s of cocaine in a dose-dependent manner, with larger doses producing m ore disruption. A constant dose of cocaine was then injected prior to every session for 40 days. Some subjects received a relatively small d ose, some received a medium-sized dose, and others received a large do se. Subsequently, dose-effects were reassessed via once-weekly probe i njections, with every other session continuing to be preceded by injec tion of the daily dose of cocaine. Then a different dose of cocaine wa s administered daily for 40 more days, after which the dose-effect fun ction was redetermined in like manner In general, tolerance to cocaine -Induced response-rate reductions was most likely to develop when (a) the repeatedly-administered dose of cocaine was relatively small (even without acute effect on keypecking) and (b) the subject's keypecking was disrupted by smaller doses of cocaine in the initial dose-effect a ssessment. Tolerance was generally observed as a shift in the dose-eff ect function that, in several cases, could be eliminated by increasing the magnitude of the daily administered dose. In addition, every subj ect's rate of keypecking following saline injections was lowered after daily exposure to cocaine. These results (a) are partially consistent with the reinforcement-loss account of tolerance to cocaine-induced b ehavioral disruptions, and (b) support previous observations of withdr awal symptoms following cessation of extended exposure to cocaine.