title: In vivo occupancy of D2 dopamine receptors by 7-OH-DPAT.
abstract: 7-OH-DPAT has been shown to exhibit selectivity between D2 and D3 dopamine receptors in a variety of in vitro assay systems. Although the drug has been used in a variety of studies to evaluate the behavioral effects of D3 receptor stimulation, the in vivo D2/D3 selectivity of the compound has not been determined. In this study, protection against inactivation by EEDQ was used as a measure of in vivo occupancy of D2 receptors by behaviorally relevant doses of 7-OH-DPAT (0.03-10 mg/kg, s.c.) in adult, male Sprague-Dawley rats. Ex vivo [3H]spiperone binding was then determined in striatal membranes. 7-OH-DPAT protected against inactivation of D2 receptors with an ED50 value of 11 mg/kg. Significant protection of D2 receptors was observed at doses of 1 mg/kg and above. These data suggest that stimulation of D2 receptors contributes to the pharmacological effects of 7-OH-DPat when administered at doses above 0.3 mg/kg (s.c.).
authors.affiliation: Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City 66160-7417, USA.
authors.forename: B
authors.initials: B
authors.lastname: Levant
authors.forename: G N
authors.initials: GN
authors.lastname: Bancroft
authors.forename: C M
authors.initials: CM
authors.lastname: Selkirk
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
chemical_list: D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D013764:Tetrahydronaphthalenes; C031349:7-hydroxy-2-N,N-dipropylaminotetralin