EFFECTS OF THE D-3 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 preferrin g dopamine (DA) agonist pramipexole (10-500 mu g/kg) showed dose-relat ed 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 slee p 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 RE MS were decreased after the 500 mu g/kg dose during the second recordi ng 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 increas e of REMS induced by pramipexole. Furthermore, the highest doses (500- 1000 mu g/kg) of the DA antagonist effectively antagonized the increas e 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 re verted 2 h later. Pramipexole (30 and 500 mu g/kg) did not significant ly affect striatal DA release during the first two hours following dru g administration, as measured by microdialysis. It is tentatively sugg ested that D-3 receptor could be involved in the pramipexole-induced i ncrease of sleep and reduction of locomotor activity. On the other han d, 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.