title: 7-OH-DPAT and PD 128907 selectively activate the D3 dopamine receptor in a novel environment.
abstract: The D3 dopamine receptor is expressed primarily in limbic brain areas, and appears to play an inhibitory role in rodent locomotor behavior. Evidence suggests a potential role for the D3 receptor in the pathology of neuropsychiatric disease. Progress in elucidating D3 receptor function has been hampered, however, by a lack of well-characterized, selective ligands and by conflicting information regarding the behavioral phenotype of D3 receptor knockout mice. Here, we describe studies evaluating the behavioral effects of (+/-)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) and PD 128907, two D3 receptor agonists whose in vivo selectivity has been a topic of considerable controversy. We demonstrate that both compounds inhibit locomotion under novel environmental conditions in wild-type (WT) mice, but are without measurable behavioral effect under identical conditions in D3 receptor knockout mice. Additionally, we demonstrate that at low, D3 selective doses, these compounds are without behavioral effect in both WT and D3 receptor knockout mice that have acclimated to the testing environment. These findings suggest that D3 receptor stimulation inhibits novelty-stimulated locomotion, and establish conditions for the use of 7-OH-DPAT and PD 128907 as D3 receptor agonists in vivo. Potential implications of these observations are discussed.
authors.affiliation: Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati, OH, USA.
authors.forename: Laurel M
authors.initials: LM
authors.lastname: Pritchard
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Logue
authors.forename: Scott
authors.initials: S
authors.lastname: Hayes
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Welge
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.forename: S Paul
authors.initials: SP
authors.lastname: Berger
authors.forename: Neil M
authors.initials: NM
authors.lastname: Richtand
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004777:Environment; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D009154:Mutation / Q000235:genetics; D010078:Oxazines / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000235:genetics; D050637:Receptors, Dopamine D3; D013268:Stimulation, Chemical; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
chemical_list: D001578:Benzopyrans; D018491:Dopamine Agonists; C493594:Drd3 protein, mouse; 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; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D004298:Dopamine