Reinforcing effects of caffeine, ephedrine, and their binary combination in rats

The reinforcing effects of caffeine, ephedrine, and caffeine + ephedrine combinations were tested in rats maintained to self-administer 0.5 mg/kg/injection of cocaine in daily 4 h limited access periods. The dose-response relationship for cocaine demonstrated a a typical inverted U-shaped function. The dose-dependent administration of cocaine was stable over the 3-day substitution epochs. Similar to earlier reports, neither caffeine nor ephedrine engendered stable patterns of self-injections. Combinations of caffeine + ephedrine produced biphasic patterns of administration only on the first day of substitution. Days 2 and 3 of the caffeine-ephedrine substitution periods engendered variable and inconsistent reinforcer deliveries that did not significantly differ from saline substitution tests. These reduced patterns of self-administered caffeine-ephedrine combinations were not attributed to behavioral toxicity. Progressive-ratio tests demonstrated rank ordered break points of: food > cocaine > caffeine-ephedrine combination = caffeine = ephedrine = saline. Caffeine-ephedrine pretreatments failed to show any significant change in the administration of the maintenance dose of cocaine except at the highest combination dose tested. Although previous data from this laboratory demonstrated symmetrical crossgeneralization between the discriminative effects of caffeine-ephedrine combinations and cocaine (5,6), the present data suggest limited reinforcing effects of these combinations in rats. (C) 1998 Elsevier Science Inc.