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.
Integrative Neuroscience Unit, Behavioral Neuroscience Laboratory, Division of Intramural Research, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.
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Rea
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Rothman
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Shippenberg
D000818:Animals; D002755:Choice Behavior / Q000187:drug effects* / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005277:Fenfluramine / Q000494:pharmacology*; D008297:Male; D010645:Phentermine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology
D005277:Fenfluramine; D010645:Phentermine