Time course for the effects of cocaine on fixed-ratio water-reinforced responding in rats

Four male rats performed during 35-min sessions under a schedule that arranged water delivery (0.04 ml) after every fortieth response. Cocaine (1.0-16.0 mg per rat, i.p.) was administered 15 min, 30 min, 60 min or 120 min prior to a session. When given 15 min prior to a session, cocaine (1.0-8.0 mg) in all rats produced dose-related decreases in responding. The largest dose, when given 15 min pre-session to two rats, almost completely suppressed responding. Lengthening the time between drug injection and test session attenuated the rate-decreasing effects of cocaine (1.0-8.0 mg), but did not affect the almost complete suppression of performance seen with the largest dose. Small doses (1.0-4.0 mg) had no effect on the pause in responding that occurred after water delivery. The 8.0-mg dose lengthened the pause by approximately 9000% and 650% when given 15 and 30 min prior to a session, respectively, but by less than 50% when given 60 or 120 min pre-session. Cocaine effects depend on the dose as well as the time of its administration prior to testing.