The effect of repeated treatment with pramipexole on the central dopamine D3 system

The study examined the effect of pramipexole (2-amino-4,5,6,7-tetrahydro-6-propyl-aminobenzthiazole dihydrochloride; PRA), a new potent dopamine receptor agonist with the high preference for D-3 receptors, as compared to D-2 or D-4, on the central dopamine D-3 system. Experiments were conducted on male Wistar rats. PRA was injected subcutaneously. PRA given repeatedly (14 days, twice a day, in doses of 0.3 and 1 mg/kg), but not acutely, potentiated the locomotor hyperactivity induced by (+/-)-7-OH-DPAT (3 mg/kg s.c.), when given 24 h after the single or the last dose of PRA. Administration of PRA, 1 mg/kg, for 3 or 7 days produced an effect similar to that described above, whereas a dose of 0.3 mg/kg produced such an effect only after 7, but not 3, days. Repeated treatment with PRA (0.3 and 1 mg/kg, 14 days, twice daily) also enhanced the D-3 receptor binding in the islands of Calleja and nucleus accumbens (shell) - the brain region known to be rich in D-3 receptors - when [H-3]7-OH-DPAT was used as a ligand. Repeated PRA administration did not change the concentration of mRNA coding for D-3 receptors in the islands of Calleja. The obtained results indicate that - like the previously studied typical antidepressants given repeatedly - PRA increases the functional responsiveness and the binding to the brain dopamine D-3 receptors. Hence PRA may be considered as a potential antidepressant drug.