In vivo autoradiography of [H-3]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 an tagonists for D1-like dopamine receptors in rat brain using [H-3]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 D1/D5 antagonist SCH 23390 and unlabeled SCH 39166, the D2-like antagonists haloperidol or the 5-HT2 antagonist keta nserin. The bound radioactivity in the cortex, striatum. nucleus accumbens and olfactory tubercle was then quantified using an in vivo autoradiographi c procedure. The results indicated that [H-3]SCH 39166 was dose dependently displaced by the D1/D5 antagonists in regions associated with both the nig ro-striatal pathway and the mesolimbic dopamine pathway, particularly the n ucleus accumbens. Neither haloperidol nor ketanserin displaced [H-3]SCH 391 66 in any of the regions examined. The data were compared with previously p ublished data examining the in vivo binding of [H-3]SCH 39166 in rat brain homogenates. The relative values obtained were comparable to values detecte d in rat brain homogenates after in vivo binding of [H-3]SCH 39166. (C) 200 0 Elsevier Science B.V. All rights reserved.