REPEATED ADMINISTRATION OF EPHEDRINE INDUCES BEHAVIORAL SENSITIZATIONIN RATS

Systemic injection of the sympathomimetic agent ephedrine (EPH) stimul ates locomotion in drug-naive rats, an effect that may be dependent on the enantiomer of EPH employed [(-)-EPH or (+)-EPH]. The present expe riments examined the effects of repeated EPH exposure on locomotion in rats to assess whether these treatments result in drug tolerance or s ensitization. In experiment 1, adult male rats were injected once dail y with 0, 10, 20, or 40 mg/kg (-)-EPH (IP) on each of II days. Locomot or activity was assessed for 60 min after drug injection. Acute exposu re to (-)-EPH treatment increased locomotion for animals receiving 20 or 40 mg/kg, and this effect was augmented after 11 days of drug admin istration. A vehicle-only injection was given to all animals on day 12 to determine the influence of environmental cues on sensitization. On day 13, all rats were injected with 10 mg/kg cocaine HCl to assess wh ether repeated (-)-EPH exposure produced a cross-sensitization to coca ine (10 mg/kg, IP). Only rats treated repeatedly with 40 mg/kg (-)-EPH exhibited increases in cocaine-stimulated locomotion relative to sali ne-treated rats. In experiment 2, repeated exposure to (+)-EPH, 40 mg/ kg, but not 20 mg/kg, increased activity and demonstrated the developm ent of sensitization. Cross-sensitization to cocaine (10 mg/kg, TP) wa s not evident following treatment with either concentration of (+)-EPH . There was no evidence that contextual events alone played a role in the effects observed here.