Paroxetine, a Selective 5-Hydroxytryptamine Uptake Inhibitor with Antidepressant Properties, Lacks Amphetamine-like Stimulus Properties in an Operant Drug Discrimination Bioassay in Rodents

The data confirm earlier studies which suggested that some antidepressants may possess abuse potential because of their ability to induce amphetamine‐like internal states, while paroxetine is devoid of such properties.

Abstract

To evaluate whether the novel antidepressant paroxetine has any possible amphetamine-like actions, rats were trained to discriminate (+)-amphetamine sulphate in a standard two lever operant drug discrimination (DD) procedure using a fixed ratio 10 schedule of food reinforcement with a quantal, lever selection, index of the amphetamine stimulus. The 'training' dose of amphetamine was 1 mg kg-1, i.p. Rats trained with this dose of amphetamine (n = 15) learned the drug discrimination rapidly over 30 training sessions and discriminative performance in these animals was subsequently maintained at a high level of accuracy (90% correct) over a prolonged time. In tests in these trained animals, amphetamine itself and the antidepressant agents nomifensine and tranylcypromine all produced clear, unequivocal dose-related generalization to amphetamine with ED50s of 0.2, 0.5 and 1.6 mg kg-1 respectively (as determined by probit analyses). In tests with paroxetine hydrochloride it was established that, over the dose range 0.3 to 10 mg kg-1, no evidence was seen of generalization to the amphetamine stimulus. These data confirm earlier studies which suggested that some antidepressants may possess abuse potential because of their ability to induce amphetamine-like internal states. In contrast, paroxetine is devoid of such properties.