Tolerance to cocaine's effects following chronic administration of a dose without detected effects on response rate or pause.

Abstract

To observe tolerance to drug effects on operant behavior, the dose that researchers have often selected for chronic administration is one that disrupts, but does not abolish, responding. Some evidence suggests that tolerance may develop after chronic administration of relatively smaller doses. The purpose of the present experiment was to assess systematically effects of chronic administration of a dose without detected effect on responding. Specifically, response rates and post-reinforcement pauses of five pigeons key pecking under a three-component multiple fixed-ratio schedule of food reinforcement were observed under chronic cocaine administration. We evaluated the effects of a range of doses (1.0 mg/kg to 17.0 mg/kg) during acute administration. The largest dose that failed to alter responding acutely then was administered chronically (1.0 mg/kg for 1 pigeon, 3.0 mg/kg for 3 pigeons, and 5.6 mg/kg for 1 pigeon). After 30 consecutive sessions of chronic administration, smaller and larger doses occasionally were substituted for the chronic dose. Pigeons then received pre-session saline administration for 30 consecutive sessions, and the post-chronic effects of the series of doses on responding were determined. All subjects developed tolerance to doses of cocaine that initially had caused large decreases in rate, with the magnitude of the effects varying across components of the multiple schedule and subjects. Specifically, tolerance generally was greatest in the components with smaller ratios. Following post-chronic saline administration, tolerance was usually diminished. Overall, the results demonstrate that under these conditions, repeated experience with disruptive effects of cocaine on food-maintained responding is not a necessary factor in the development of tolerance.