Amphetamine enantiomers and rat consummatory behavior: a new perspective.

The anorectic actions of amphetamine have been known for over forty years, yet the precise relationship(s) between the enantiomeric forms of the drug and anorexia is not clearly understood. Previous studies have utilized primarily racemic amphetamine or its d-isomer in the analysis of feeding behavior. In the present investigation, a detailed examination of the effects of single and repeated equiactive doses of d- and l-amphetamine on food consumption by adult male rats was undertaken with emphasis on aspects of tolerance development. Weight loss and pattern of daily food intake differed depending upon the isomer, dose, and degree of tolerance. Two types of tolerance were seen with both isomers, an initial tolerance with a decrease in efficacy between days 1 and 2, and a later gradual decrease in efficacy over 12 days of repeated dosage. Rats tolerant to the anorectic effects of d-amphetamine were only minimally affected when challenged with an equiactive anorectic dose of l-amphetamine, while rats tolerant to the anorectic effects of l-amphetamine showed a significantly depressed food intake and modified eating pattern when challenged with an equiactive dose of d-amphetamine. Therefore two-way cross tolerance, as previously assumed, does not completely exist between low equiactive doses of d- and l-amphetamine.