Attenuation of cocaine-induced response-rate increases during repeated administration despite increases in rate of...

Repeated administration of cocaine often results in tolerance to its effects on operant behavior. The tolerance is often associated with an initial drug effect that results in loss of reinforcement. Cocaine can also produce effects that result in a gain of reinforcement, and it is not known if tolerance will be observed in such a circumstance. The present experiments investigated whether tolerance would develop when cocaine was administered repeatedly to subjects who experienced an increase in the frequency of reinforcement when cocaine was administered acutely. Pigeons were trained to peck a response key under fixed-ratio schedules of food presentation. The ratio value for each pigeon was chosen such that performance indicated that the ratio was relatively large, and produced "ratio strain.". Cocaine was administered acutely (once per week), and then subsequently a dose was chosen and administered before each session. Once performance under the daily drug regimen was stable, other doses occasionally were substituted for the usual daily dose. Acute administration of cocaine (0.3-10.0 mg/kg) revealed substantial increases of 100% or more in response rate, and therefore equivalent increases in rate of food presentation, at some doses. That finding permitted examination of the role of drug-induced increases in rate of reinforcement during repeated administration of a response-rate-increasing dose. Repeated, daily administration of a rate-increasing dose resulted in attenuation of the effects of that dose, and subsequent administration of other doses that previously had increased response rates revealed that these doses, too, had lost their ability to increase rates. That is, "tolerance" developed to the rate-increasing effects, even though the rate increases were associated with more frequent access to food. These findings suggest that "reinforcement gain" may not be sufficient to prevent tolerance from developing to effects of cocaine on operant behavior.