Stability of cocaine dose–response functions at different inter-dose intervals

Past research has found that daily administration of cocaine can lead to tolerance to its behavioral effects, and that tolerance can develop even when the dose is varied from day to day. The present experiment examined effects of administering varied doses of cocaine at a variety of inter-dose intervals ranging from once per week to everyday. Pigeons pecked on a fixed-ratio 20 schedule of reinforcement. A dose–response function for cocaine was assessed eight consecutive times during each of four phases of the experiment to assess the stability of effects of each dose. In Phase 1, subjects were administered a dose of cocaine or saline vehicle every seventh day. One subject developed tolerance by the end of this phase and was not studied further. In Phase 2, doses were administered every fourth day. During Phase 3, doses were administered every 2 days. In the final phase, doses were administered everyday. Dose–response curves were generally similar both within and across phases, regardless of inter-dose interval. No subjects developed tolerance during Phases 2, 3, and 4, suggesting that some aspect of the drug regimen prevented the development of tolerance when cocaine was given frequently.