Effect of time-out duration on the reinforcing strength of cocaine assessed under a progressive-ratio schedule in rhesus monkeys.

Progressive-ratio (PR) schedules of reinforcement have provided valuable information regarding the reinforcing strength of cocaine and the underlying neurobiological mechanisms. Parametric manipulations, such as altering time-out (TO) values, can affect the shape of the cocaine dose-response curve. Earlier studies have used PR schedules with widely varying parameters, thus complicating comparisons across experiments. This study evaluated the reinforcing strength of cocaine (0.005-0.9 mg/kg) as a function of post-reinforcement TO duration (5, 10, 30, or 60 min) under a PR schedule in rhesus monkeys. Daily sessions ended when 2 h elapsed without an injection; the breakpoint value was defined as the total number of injections. When the TO was 10 min, the relationship between cocaine dose and the number of injections received (i.e. BP) was characterized by an inverted U-shaped curve in all monkeys. Increasing the TO to 30 min resulted in a rightward shift of the ascending limb of the dose-response curve, but did not affect self-administration of higher doses. The number of injections received of a low cocaine dose was not further increased when the TO was shortened to 5 min, nor did increasing the TO to 60 min alter self-administration of the highest tested dose. These results suggest that drug accumulation plays a role in determining the reinforcing strength of low and intermediate cocaine doses under PR schedules. However, the reinforcing strength of higher cocaine doses was unaffected by manipulating TO, suggesting that the BP value is a useful measure of reinforcing strength.