Amphetamine enantiomers and rat consummatory behavior: a new perspective

Area of Science:

• Pharmacology
• Neuroscience
• Behavioral Science

Background:

• The anorectic effects of amphetamine are well-documented but the specific roles of its enantiomers, d-amphetamine and l-amphetamine, remain unclear.
• Prior research predominantly used racemic amphetamine or d-amphetamine, limiting understanding of individual enantiomer contributions to feeding behavior.

Purpose of the Study:

• To investigate the differential effects of d- and l-amphetamine on food consumption and tolerance development in adult male rats.
• To elucidate the extent of cross-tolerance between equiactive doses of d- and l-amphetamine.

Main Methods:

• Adult male rats were administered single and repeated equiactive doses of d- and l-amphetamine.
• Food consumption, weight loss, and eating patterns were monitored to assess anorectic effects and tolerance.
• Cross-tolerance was evaluated by challenging rats tolerant to one enantiomer with the other.

Main Results:

• Weight loss and daily food intake patterns varied significantly based on the amphetamine isomer, dose, and developed tolerance.
• Two distinct phases of tolerance were observed for both isomers: an initial rapid decrease in efficacy and a subsequent gradual decline.
• Rats tolerant to d-amphetamine exhibited minimal response to l-amphetamine, while those tolerant to l-amphetamine showed significant food intake reduction when given d-amphetamine.

Conclusions:

• D- and l-amphetamine exhibit distinct anorectic profiles and tolerance development patterns.
• Complete two-way cross-tolerance between equiactive doses of d- and l-amphetamine does not exist, contrary to prior assumptions.