Paroxetine, a selective 5-hydroxytryptamine uptake inhibitor with antidepressant properties, lacks amphetamine-like stimulus properties in an operant drug discrimination bioassay in rodents.
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.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D005260:Female; D005425:Flicker Fusion / Q000187:drug effects; D009627:Nomifensine / Q000494:pharmacology; D017374:Paroxetine; D010880:Piperidines / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014191:Tranylcypromine / Q000494:pharmacology
D000928:Antidepressive Agents; D010880:Piperidines; D012702:Serotonin Antagonists; D009627:Nomifensine; D014191:Tranylcypromine; D017374:Paroxetine; D003913:Dextroamphetamine