Effects of the D3 preferring dopamine agonist pramipexole on sleep and waking, locomotor activity and striatal dopamine release in rats.
Quantitation of 2 h sessions after administration of the D3 preferring dopamine (DA) agonist pramipexole (10-500 microg/kg) showed dose-related effects on wakefulness (W), slow wave sleep (SWS) and REM sleep in rats. The 30 microg/kg dose of the DA agonist increased SWS and REM sleep and reduced W during the first recording hour, while the 500 microg/kg dose augmented W. On the other hand, W was increased while SWS and REMS were decreased after the 500 microg/kg dose during the second recording hour. The mixed D2- and D3 receptor antagonist YM-09151-2 (30-500 microg/kg), which per se affected sleep variables prevented the increase of REMS induced by pramipexole. Furthermore, the highest doses (500-1000 microg/kg) of the DA antagonist effectively antagonized the increase of W and reduction of SWS induced by the 500 microg/kg dose of the DA agonist. Pramipexole (30-100 microg/kg) induced a decrease of locomotor activity during the 2 h recording period. In addition, the 500 microg/kg dose gave rise to an initial reduction of motor behavior which was reverted 2 h later. Pramipexole (30 and 500 microg/kg) did not significantly affect striatal DA release during the first two hours following drug administration, as measured by microdialysis. It is tentatively suggested that D3 receptor could be involved in the pramipexole-induced increase of sleep and reduction of locomotor activity. On the other hand, the increase of W and of motor behavior after relatively high doses could be related to activation of postsynaptic D2 receptor.
Lagos
P
P
Division of Cellular Biology, Institute of Biological Sciences Clemente Estable, Montevideo, Uruguay.
Scorza
C
C
Monti
J M
JM
Jantos
H
H
Reyes-Parada
M
M
Silveira
R
R
Ponzoni
A
A
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology; D052160:Benzothiazoles; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D000077487:Pramipexole; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3; D012890:Sleep / Q000187:drug effects; D012895:Sleep, REM / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D014851:Wakefulness / Q000187:drug effects
D001549:Benzamides; D052160:Benzothiazoles; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493595:Drd3 protein, rat; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013844:Thiazoles; D000077487:Pramipexole; C030265:nemonapride; D004298:Dopamine