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.
Rea
W P
WP
Integrative Neuroscience Unit, Behavioral Neuroscience Laboratory, Division of Intramural Research, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.
Rothman
R B
RB
Shippenberg
T S
TS
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