Effects of dose and session duration on cocaine self-administration in rats

Previous studies showed that an extended 6-h session duration produced an increasing rate of cocaine self-administration in rats. The present study further investigated the effect of dose and session duration on cocaine self-administration. Eight groups of rats (4 doses x 2 session durations) self-administered one of four cocaine doses (0.25, 0.5, 1, and 2 mg/kg/injection) in either 1- or 6-h sessions under a fixed-ratio schedule. In another experiment, two other groups of rats self-administered 0.5 mg/kg/injection of cocaine in either 3- or 12-h sessions. Cocaine self-administration increased at all doses in 6-h sessions but not in 1-h sessions. Cocaine intake (milligram/kilogram) reached an asymptote earlier at a higher dose, but the rate of responding increased faster when the dose was lower. In ShA rats, the cocaine dose-response function was higher in rats at the two higher unit doses than at the lower doses. Cocaine self-administration increased in 6- and 12-h sessions, but not in 1- and 3-h sessions. The increase in self-administration was faster and greater in 12-h sessions than 6-h sessions. The data suggest that cocaine self-administration increases at various doses with prolonged access and that an increase in the rate of responding is positively and inversely associated with session duration and unit dose, respectively. Results also imply that cocaine intake reaches a ceiling faster at high doses even under short session duration. Therefore, high doses or prolonged access to cocaine are more likely to result in a pattern of cocaine intake that reflects compulsive use.