Intra-accumbens infusion of D3 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 mug/0.5 mul) 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 mug/0.5 mul) was studied. Pretreatment with either PD 128907 or 7-OH-DPAT (3 mug) reduced DA-induced hyperactivity. Local infusion of B-HT 920 (3 mug) 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. (C) 2000 Elsevier Science Inc. All rights reserved.