Cumulative dose-response curves in behavioral pharmacology

Cumulative dose-response curves have been widely used in many areas of pharmacology. To date, the applicability of cumulative dose-response curves has not been assessed in behavioral pharmacology. To determine the feasibility of this procedure, mice were trained to respond under a multiple time-out 5 min, fixed-ratio 30 (mult TO 5, FR 30) schedule of reinforcement. The FR 30 component consisted of 15 presentations of an FR 30 schedule of reinforcement. At the start of each TO 5 component, an intraperitoneal (IP) injection was given, and the effect on the response rate during the following 15 presentations of the FR 30 schedule was assessed. d-Amphetamine (0.3--30 mu moles/kg), pentobarbital (3-300 mu moles/kg), morphine (1-100 mu moles/kg), ketamine (3-300 mu moles/kg), and phencyclidine (1-100 mu moles/kg) all produced dose-related decreases in FR responding. In each case the lowest dose tested was without effect, and the highest dose tested essentially eliminated responding. As a control, the normal 4th dose in the ascending series of each drug was given preceded by 3 saline injections. Whether this dose of each drug was preceded by 3 separate saline injections or by 3 lower ascending doses of the same drug, the observed effect was identical. Five consecutive saline injections during the experimental session were without effect. The application of this procedure should greatly decrease the time required to examine the behavioral effects of a wide range of doses.