Effects of fixed-interval duration on the development of tolerance to decreased responding by l-nantradol.

Key pecking of pigeons was maintained under a chained schedule in which the first response after 2 h (fixed interval) was followed by the opportunity to obtain food after sequences of 30 responses (fixed ratio), and animals received acute injections of l-nantradol (0.001-0.1 mg/kg). Smallest doses were ineffective; largest doses decreased all responding; and intermediate doses decreased fixed-interval, but not fixed-ratio, responding. When animals subsequently received daily administration of 0.1 mg/kg l-nantradol prior to experimental sessions, initially decreased fixed-interval responding did not recover during 21 sessions of l-nantradol administration, whereas fixed-ratio responding was demonstrated on several occasions by automatic advancement to the fixed-ratio component. When the schedule was changed so that the same total amount of food was available after ten shorter fixed intervals, fixed-interval responding resumed within a single session, and when the schedule was changed back so that all food was available only after 2 h had elapsed, fixed-interval responding diminished within a few sessions and virtually no responding occurred for 21 additional sessions. The behavioral effects of chronic l-nantradol depended on both the schedule and the parameter of reinforcement.