Effect of fenfluramine and nicotine upon a stimulant-depressant continuum

Rats were rapidly trained to discriminate between 0.8 mg/kg d-amphetamine and 6 mg/kg pentobarbital in a two-lever food-motivated operant task by imposing the drug states from the earliest stage of training. Once trained, rats were administered lower doses of each of the training drugs and both d-amphetamine and pentobarbital were observed to produce dose-responsive effects upon discriminative performance. When graphically represented, the dose-response curves were shown to be parallel suggesting a common site and/or mechanism of action. Administration of fenfluramine (1.5 and 2.25 mg/kg) produced pentobarbital-appropriate responding, whereas the injection of three doses of nicotine (0.1-0.4 mg/kg) resulted in amphetamine-like discriminative responding. Inspection of dose-response curves suggested that fenfluramine produces its pentobarbital-like effects by acting differently than does pentobarbital and, although nicotine produces amphetamine-like effects, it acts by a different mechanism than does amphetamine.