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 D3 receptors, as compared to D2 or D4, on the central dopamine D3 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 (3mg/kg s.c.), when given 24h 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 D3 receptor binding in the islands of Calleja and nucleus accumbens (shell)--the brain region known to be rich in D3 receptors--when [3H]7-OH-DPAT was used as a ligand. Repeated PRA administration did not change the concentration of mRNA coding for D3 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 D3 receptors. Hence PRA may be considered as a potential antidepressant drug.
Maj
J
J
Institute of Pharmacology, Polish Academy of Sciences, Krakow.
Rogói
Z
Z
Margas
W
W
Kata
M
M
Dziedzicka-Wasylewska
M
M
D000818:Animals; D052160:Benzothiazoles; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D017403:In Situ Hybridization; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D000077487:Pramipexole; D012333:RNA, Messenger / Q000235:genetics; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D050637:Receptors, Dopamine D3; D050638:Receptors, Dopamine D4; D013764:Tetrahydronaphthalenes / Q000493:pharmacokinetics; D013844:Thiazoles / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014316:Tritium
D052160:Benzothiazoles; D018491:Dopamine Agonists; C493595:Drd3 protein, rat; C493601:Drd4 protein, rat; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D013844:Thiazoles; D014316:Tritium; D050638:Receptors, Dopamine D4; D000077487:Pramipexole; C031349:7-hydroxy-2-N,N-dipropylaminotetralin