Effects of cocaine alone and in combination with prazosin or ondansetron on multiple fixed-interval fixed-ratio...

Three pigeons were trained to respond on a two-component multiple schedule in which the components alternated regularly. In one component of the schedule, food was presented when the pigeon successfully completed a fixed-interval 120-s schedule within 150 s. In the other component of the schedule, food presentation occurred when the pigeon managed to complete a fixed-ratio 30 schedule within 30 s. Once responding had stabilized under both components of the schedule, pigeons were challenged with different doses of cocaine alone or cocaine in combination with 1.0 mg/kg prazosin (a selective alpha 1-adrenergic antagonist) or 0.10 or 0.50 mg/kg ondansetron (a selective 5-hydroxytryptamine3 antagonist). All drugs were injected intramuscularly 5 min before the start of selected experimental sessions. For two subjects, low doses of cocaine increased the low response rates maintained by the fixed-interval schedule while decreasing the high rates maintained by the fixed-ratio schedule. At intermediate doses, both high and low rates decreased but higher rates were more susceptible to disruption than low rates. The highest doses of cocaine completely eliminated responding in both schedule components. The high-rate behavior of the third subject was not affected by low or intermediate doses of cocaine, while low rates decreased at doses up to 5.6 mg/kg. The higher doses of cocaine eliminated responding in this subject as well. Prazosin and both doses of ondansetron antagonized the behavioral effects of cocaine at doses that ranged from 1.0-3.0 mg/kg. Redetermination of the dose-effect curve for cocaine at the conclusion of the experiment revealed that the curve had significantly shifted to the right.