The dopamine D-1 receptor agonist SKF-82958 serves as a discriminative stimulus in the rat

We examined the discriminative stimulus effects of the high-efficacy dopami ne D-1 receptor agonist (+/-)6-chloro-7,8-dihydroxy-3-allyl-phenyl-2,3,4,5- tetrahydro-1 H-3benzazepine hydrobromide (SKF-82958) in rats trained to dis criminate SKF-82958 (0.03 mg/kg) from vehicle in a two-lever food-reinforce d drug discrimination task. SKF-82958 produced dose-related increases in re sponding to the SKF-82958 appropriate lever with full substitution occurrin g at the training dose. Pretreatment with the dopamine D-1/D-5 receptor ant agonist (-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2hydroxy-N-methyl-5H-be nzo-[d]naphtho-{2,1-b}azepine (SCH-39166) (0.01 mg/kg) attenuated the discr iminative stimulus effects of SKF-82958. Pretreatment with the dopamine D-2 receptor antagonist raclopride (0.03 mg/kg) had no effect. The high-effica cy dopamine D-1 receptor agonist R(+)6chloro-7,8-dihydroxy-1-phenyl-2,3,4,5 -tetrahydro-1H-3-benzazepine hydrobromide (SKF-81297) fully substituted for SKF-82958, whereas the low-efficacy dopamine D-1 receptor agonist (+/-)1-p henyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride (SKF-383 93) produced only partial substitution. The dopamine D2 receptor agonist tr ans-(+/-)-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1 H-propyl-1 H-pyrazolo[3,4- g]quinoline dihydrochloride (quinpirole) and the indirect dopamine agonist cocaine did not substitute fully for the SKF-82958 discriminative stimulus cue. These results demonstrate that the high-efficacy dopamine D-1 receptor agonist SKF-82958 can serve as an effective discriminative stimulus in the rat, and that these effects are mediated by a dopamine D-1-like receptor m echanism. (C) 2000 Elsevier Science B.V. All rights reserved.