DEVELOPMENT OF TOLERANCE IN PIGEONS TO BEHAVIORAL EFFECTS OF A NEW BENZOPYRAN DERIVATIVE

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

Pigeons were trained under a multiple fixed-ratio, fixed-interval schedule of food presentation until their performance in daily sessions was consistent from day to day. Effects of a new nitrogen-containing benzopyran derivative, SP-1, on the performance was then studied. Doses of SP-1 up to 0.3 mg/kg had little effect on rates of responding; higher doses reduced responding, until a dose of 3.0 mg/kg abolished responding in both components of the schedule and produced ataxia. When the 3.0 mg/kg dose of SP-1 was injected daily, responding was suppressed during each of the first three days, but on succeeding days responding progressively recovered. The daily dosage was then increased to 10.0 mg/kg, then to 17.0 mg/kg and finally to 30.0 mg/kg of SP-1. After the first few days the mean rate of responding was always above 50% of control rate and responding after the last injection of 30.0 mg/kg, ending 17 daily drug injections, was essentially normal. After a period of 30 days without drug, 30 mg/kg of SP-1 still did not suppress responding, showing the persistence of a strong tolerance to the suppressive behavioral effects of the drug. After a period of 100 days without drug, however, a single injection of 30.0 mg/kg again suppressed responding and caused ataxia in the pigeons.