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 D-3 preferring dopamine (DA) agonist pramipexole (10-500 mu g/kg) showed dose-related effects on wakefulness (W), slow wave sleep (SWS) and REM sleep in rats. The 30 mu g/kg dose of the DA agonist increased SWS and REM sleep and reduced W during the first recording hour, while the 500 mu g/kg dose augmented W. On the other hand, W was increased while SWS and REMS were decreased after the 500 mu g/kg dose during the second recording hour. The mixed D-2- and D-3 receptor antagonist YM-09151-2 (30-500 mu g/kg), which per se affected sleep variables prevented the increase of REMS induced by pramipexole. Furthermore, the highest doses (500-1000 mu g/kg) of the DA antagonist effectively antagonized the increase of W and reduction of SWS induced by the 500 mu g/kg dose of the DA agonist. Pramipexole (30-100 mu g/kg) induced a decrease of locomotor activity during the 2 h recording period. In addition, the 500 mu g/kg dose gave rise to an initial reduction of motor behavior which was reverted 2 h later. Pramipexole (30 and 500 mu g/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 D-3 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 D-2 receptor. (C) 1998 Elsevier Science B.V./ECNP.