Phentermine+fenfluramine produce cocaine-like discriminative cues.

Drug discrimination studies were conducted in six male Sprague-Dawley rats trained to discriminate the interoceptive cues produced by 10 mg/kg cocaine in an effort to investigate if there is stimulus generalization to phentermine or phentermine + fenfluramine. Once having reached criterion performance, these rats were tested with lower doses of cocaine and generated a typical dose-response curve allowing for calculation of an ED50 value: 2.798 mg/kg. Testing of phentermine in doses of 1.25-5.0 mg/kg indicated generalization with the highest dose producing 80% cocaine-appropriate responding and allowing for an ED50 value of 2.356 mg/kg. When the phentermine doses were tested in combination 2.0 mg/kg fenfluramine, however, there was an increase in the discriminability of the highest phentermine dose and a slight decrease in the ED50 value of the combination. Thus, administration of phentermine + fenfluramine, having both dopamine-releasing and serotonin-releasing properties, respectively, may mimic the neurochemical activity by which cocaine acts in the central nervous system and may possibly allow for cocaine-like effects as these two drugs see increased use in obesity control.