Evaluation of the conditioned reinforcing effects of phentermine and fenfluramine in the rat: Concordance with clinical studies

An unbiased place-preference conditioning procedure was used to characterize the conditioned reinforcing effects of phentermine (PHEN), fenfluramine (FEN), and their combination (PHEN/FEN) in previously drug-naive rats. Animals exhibited marked preferences for an environment previously associated with the administration of phentermine. The minimum dose producing a significant effect was 3.0 mg/kg. In contrast, FEN produced dose-related place aversions. In animals which received a subthreshold dose of FEN in combination with a dose of PHEN that produced a conditioned place preference, no preference or aversion for the drug-paired place was seen. Similarly, no significant conditioning in response to administration of PHEN (3.0 mg/kg) and FEN (3.0 mg/kg) was seen. The failure of PHEN/FEN to produce conditioned reinforcing effects is in line with recent clinical studies, and suggests that PHEN/FEN and drug combinations sharing the same neurochemical mechanisms of action will have low potential for abuse.