Amineptine improves the performance of dogs in a complex temporal regulation schedule

Amineptine is a tricyclic antidepressant with activating properties, that stimulates spontaneous locomotor activity in rodents and elevates mood in humans. It mainly inhibits dopamine uptake and weakly increased dopamine release. Formulating the hypothesis that this drug would decrease waiting capacity, we decided to test amineptine in a Differential Reinforcement of Response Duration schedule (DRRD 9 s Limited Hold 1.5 s) in the dog. The drug was administered orally at 2.5, 5.0, 7.5, 10 and 20 mg/kg, 1 h before the experimental session. Between 2.5 and 10 mg/kg, amineptine improved the performance by increasing the response (nonsignificantly) and reinforcement (significantly) rates and by increasing the peak of correct responses (significantly). The inverse effect was measured for the reinforcement rate (nonsignificantly) and for the peak of correct responses (significantly) at the dose of 20 mg/kg. These results were compared to those obtained with other classes of drugs, like neuroleptics, barbiturates or anxiolytics, that disturbed the performance, and particularly with low doses of neuroleptics, which also increase the dopamine release. The positive effects of amineptine on performance (2.5-10 mg/kg) were related to its inhibitory effect on dopamine uptake and discussed in terms of improved vigilance and attention, increase of waiting capacity, improved anticipation, and cognitive enhancement.