Decreased locomotor activity after microinjection of dopamine D2/D3 receptor agonists and antagonists into lobule 9/10 of the cerebellum: a D3 receptor mediated effect?
The restricted localization of dopamine (DA) D3 receptors in the rat cerebellum lobule 9/10 appears to provide a method for investigating the in vivo selectivity of dopaminergic compounds for the D3 receptor subtype. Sprague-Dawley rats implanted with a cannula aimed at lobule 9/10 were microinjected with DA receptor ligands and immediately placed into activity chambers to record their spontaneous locomotor activity for short term (0 to 20 min) and delayed (20 to 40 min) effects. The DA D2/D3 receptor agonists quinelorane (0.1 to 2.5 microg) and 7-OH-DPAT (0.1 to 10 microg) decreased locomotor activity in the first 20 min post-microinjection. In contrast, the DAD1, receptor agonist 6-Br-APB (0.1 to 10 microg) did not affect locomotor activity during this time period, but markedly increased locomotion between 20 and 40 min at the highest dose tested. The DA receptor antagonists haloperidol and raclopride (1 to 10 microg) were also found to reduce locomotor activity. Furthermore, quinelorane and 7-OH-DPAT, but not haloperidol, when microinjected into lobules 1/2 or 6/7 (where no DA D3 receptors have been detected) decreased locomotor scores. These results show that both DA receptor agonists and antagonists decrease locomotor activity when microinjected into lobule 9/10 of the cerebellum. Additionally, DA receptor agonists can reduce spontaneous locomotion when microinjected outside of lobule 9/10. This would suggest that, at least for quinelorane and 7-OH-DPAT, the locomotor decreasing effects following microinjection into cerebellar lobule 9/10 may not be mediated by activity at DA D3 receptors, and that this behavioural assay is unlikely to provide a means for studying the in vivo pharmacology of the DA D3 receptor.
Boulay
D
D
Synthélabo Recherche, Bagneux, France.
Depoortere
R
R
Perrault
G
G
Sanger
D J
DJ
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002531:Cerebellum / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493595:Drd3 protein, rat; D011804:Quinolines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; C074280:3-allyl-6-bromo-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; D020891:Raclopride; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D006220:Haloperidol; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; C047726:quinelorane