PERSISTENCE OF TOLERANCE TO EFFECTS OF COCAINE ON SCHEDULE-CONTROLLEDBEHAVIOR IN PIGEONS

Keypecking by seven pigeons, maintained by a fixed-ratio 30 schedule o f food presentation, was decreased in rate by acute pre-session admini stration of cocaine. In Part 1 (four pigeons), tolerance to the rate-s uppressing effects of cocaine developed during daily administration co nditions. Tolerance persisted (1) when daily cocaine injections were r eplaced by conditions in which cocaine was administered every other da y, then every fourth day, then every eighth day, then every 16th day, with all intervening sessions preceded by saline injections and (2) wh en daily cocaine administration was replaced abruptly by a condition i n which cocaine injections were spaced 16 days apart, with all interve ning sessions preceded by saline. In Part 2 (three pigeons), tolerance developed during intermittent administration conditions (e.g. cocaine injected every eighth day) for two subjects, and during daily adminis tration for the third subject. As in Part 1, tolerance persisted when cocaine was administered only once every 16 days. These results are co nsistent with an interpretation of tolerance based upon operant compen satory reactions to drug-induced behavioral disruptions and suggest th at a simple associationist model of tolerance to cocaine-induced respo nse rate suppression may be inadequate. The data also have practical i mplications regarding tolerance development during intermittent admini stration conditions similar to conventional acute dose-effect determin ation procedures.