Intra-accumbens infusion of D(3) receptor agonists reduces spontaneous and dopamine-induced locomotion

The present study investigated whether PD 128907 and 7-OH-DPAT, described as preferential dopamine (DA) D(3) receptor agonists, produce hypolocomotion by acting at postsynaptic dopaminergic receptors within the nucleus accumbens. Bilateral infusion of PD 128907 (1.5 and 3 microg/0.5 microl) induced a dose-dependent hypolocomotion, whereas its enantiomer, PD 128908, was inactive. Local infusion of 7-OH-DPAT and the preferential DA autoreceptor agonist, B-HT 920, at the same dose range also decreased spontaneous locomotion. In addition, both drugs induced yawning with B-HT 920 producing the greatest effect. In the second experiment, the ability of these agonists to reduce the locomotor activity induced by intra-accumbens injection of DA (10 microg/0.5 microl) was studied. Pretreatment with either PD 128907 or 7-OH-DPAT (3 microg) reduced DA-induced hyperactivity. Local infusion of B-HT 920 (3 microg) failed to antagonise the locomotor effects of DA. Altogether these findings suggest that PD 128907 and 7-OH-DPAT induce hypolocomotion by acting in part at postsynaptic DA receptors. The possible role of D(2) and/or D(3) receptors in the mediation of these effects is discussed.