Effects of ephedrine enantiomers on conditioned taste aversion and kaolin intake in rats

The ephedrine (EPH) enantiomers, (-)-EPH and (+)-EPH, have different biological activity in the rat, with the (-)-EPH enantiomer exerting a greater impact on suppression of feeding, induction of locomotion, and activation of brown adipose tissue thermogenesis. Recent studies document that (-)-EPH treatment produces an alteration of extracellular dopamine in the brain, an effect that is consistent with the locomotor-stimulating and reinforcing effects of this drug. Whether the EPH enantiomers exert aversive actions in the rat is unknown. Experiment 1 examined the impact of systemically administered (+)-EPH (0, 5, 10, or 20 mg/kg) or (-)-EPH (0, 5, 10, or 20 mg/kg) on conditioned taste aversion (CTA) in adult male rats relative to the effect of 32 mg/kg lithium chloride (LiCl). No dose of either enantiomer produced CTA, whereas strong CTA was evident for LiCl. In Experiment 2, consumption of kaolin (a nonnutritive clay) over a 24-h period was used to assess drug toxicity. Rats treated with either 0, 5, 10, 20, or 40 mg/kg (+)-EPH or 0, 5, 10, 20, or 40 mg/kg (-)-EPH did not exhibit alteration of kaolin intake. In contrast, systematic increases in kaolin intake were observed in rats after systemic administration of LiCl (0, 16, 32, 64, and 96 mg/kg). These findings suggest that the enantiomers of EPH do not exert aversive effects at behaviorally relevant doses.