REINFORCING EFFECTS OF CAFFEINE, EPHEDRINE, AND THEIR BINARY COMBINATION IN RATS

The reinforcing effects of caffeine, ephedrine, and caffeine + ephedri ne combinations were tested in rats maintained to self-administer 0.5 mg/kg/injection of cocaine in daily 4 h limited access periods. The do se-response relationship for cocaine demonstrated a a typical inverted U-shaped function. The dose-dependent administration of cocaine was s table over the 3-day substitution epochs. Similar to earlier reports, neither caffeine nor ephedrine engendered stable patterns of self-inje ctions. Combinations of caffeine + ephedrine produced biphasic pattern s of administration only on the first day of substitution. Days 2 and 3 of the caffeine-ephedrine substitution periods engendered variable a nd inconsistent reinforcer deliveries that did not significantly diffe r from saline substitution tests. These reduced patterns of self-admin istered caffeine-ephedrine combinations were not attributed to behavio ral 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 o f cocaine except at the highest combination dose tested. Although prev ious data from this laboratory demonstrated symmetrical crossgeneraliz ation between the discriminative effects of caffeine-ephedrine combina tions and cocaine (5,6), the present data suggest limited reinforcing effects of these combinations in rats. (C) 1998 Elsevier Science Inc.