In vivo autoradiography of [3H]SCH 39166 in rat brain: selective displacement by D1/D5 antagonists.
The purpose of this study was to examine the receptor occupancy of D1/D5 antagonists for D1-like dopamine receptors in rat brain using [3H]SCH 39166, a highly selective D1/D5 antagonist with low affinity for 5HT2 receptors. A single concentration of triated SCH 39166 was administered to rats, with or without competing doses of the Dl/D5 antagonist SCH 23390 and unlabeled SCH 39166. the D2-like antagonists haloperidol or the 5-HT, antagonist ketanserin. The bound radioactivity in the cortex, striatum, nucleus accumbens and olfactory tubercle was then quantified using an in vivo autoradiographic procedure. The results indicated that [3H]SCH 39166 was dose dependently displaced by the Dl/D5 antagonists in regions associated with both the nigro-striatal pathway and the mesolimbic dopamine pathway, particularly the nucleus accumbens. Neither haloperidol nor ketanserin displaced [3H]SCH 39166 in any of the regions examined. The data were compared with previously published data examining the in vivo binding of [3H]SCH 39166 in rat brain homogenates. The relative values obtained were comparable to values detected in rat brain homogenates after in vivo binding of [3H]SCH 39166.
Duffy
R A
RA
Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. ruth.duffy@spcorp.com
Hunt
M A
MA
Wamsley
J K
JK
McQuade
R D
RD
D000818:Animals; D001345:Autoradiography; D001552:Benzazepines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism; D018492:Dopamine Antagonists / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D011699:Putamen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D050641:Receptors, Dopamine D5; D013378:Substantia Nigra / Q000378:metabolism
D001552:Benzazepines; D018492:Dopamine Antagonists; C493607:Drd5 protein, rat; D017447:Receptors, Dopamine D1; C058081:ecopipam; D050641:Receptors, Dopamine D5