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.
Ouagazzal
A M
AM
Preclinical Research, Pharmaceuticals Division, F. Hoffmann-La Roche, PRPN, CH-4070, Basel, Switzerland. abdel-mouttalib.ouagazzal@roche.com
Creese
I
I
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D010078:Oxazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000502:physiology; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D001381:Azepines; D001578:Benzopyrans; D018491:Dopamine Agonists; C493595:Drd3 protein, rat; D010078:Oxazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol; C024763:talipexole; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D004298:Dopamine