ANTIDEPRESSANT EFFECTS OF PRAMIPEXOLE, A NOVEL DOPAMINE-RECEPTOR AGONIST

Pramipexole (2-amino-4,5,6,7-tetrahydro-6-propyl-amino- benzthiazole-d ihydrochloride), a new dopamine receptor agonist with preference for D -3 compared to D-2 and D-4 receptors, was tested in rats in respect of its potential antidepressant activity. In the forced swimming test th e drug under study, given three times in rats, reduced the immobility time. In the forced swimming test, joint treatment with antidepressant s (imipramine, amitriptyline) and pramipexole evoked a more potent eff ect than any of the drugs given alone; however, the locomotor hyperact ivity was weaker after joint administration. Citalopram and fluoxetine , inactive per se in the forced swimming tests, visibly enhanced the a ntidepressant-like effect of pramipexole but, on the other hand, they attenuated the locomotor hyperactivity evoked by the drug. Repeated tr eatment with pramipexole (0.3 or 1 mg/kg, twice daily for 14 days) inc reased the locomotor activity measured at 1 h after the last dose. Rep eated administration of pramipexole (as above) potentiated the D-amphe tamine- or quinpirole-induced locomotor hyperactivity. The obtained re sults indicate that, in the tests used, pramipexole evokes effects sim ilar to those of typical antidepressants and, at the same time, enhanc es their activity (the forced swimming test in rats); therefore it may be regarded as a potential antidepressant drug.