Effects of acute and chronic administration of phenobarbital and d-amphetamine on schedule-controlled behavior

The effects of acute and chronic administration of phenobarbital and d-amphetamine were determined in rats responding under a multiple fixed-interval five minute fixed-ratio 30 (mult FI 5 FR 30) schedule of food presentation. After determining the acute effects of each drug, the drugs were injected daily with one group of rats receiving the drugs before each behavioral session while another group received the drugs immediately after each daily session. After four to seven consecutive injections, tolerance developed to the effects of phenobarbital on the average rates of responding under FI and FR schedule components only if the drug was administered before each session. Tolerance was more pronounced for responding druing the terminal portions of the FI component than for responding during either the initial portions of the FI or the FR component. Evidence for a selective tolerance to the effects of the drug on responding during the final segments of the FI was also obtained in rats responding under an FI 5 schedule. In contrast, injection of d-amphetamine for seven to eight consecutive days failed to produce any tolerance to the effects of the drug on responding under mult FI 5 FR 30, FI 5, or FR 30 schedules. These results indicate that the development of tolerance to the effects of phenobarbital depended both upon the temporal relationship of the drug effects to the behavioral testing and upon the schedules controlling behavior. These findings are discussed in terms of theories of behavioral tolerance.