The D1 agonists SKF 82958 and SKF 77434 are self-administered by rats.
The reported failure of the prototypical (but partial) D1 agonist SKF 38393 to support self-administration behavior contradicts hypotheses of D1-mediated reinforcement. Here we demonstrate that rats will readily self-administer two SKF 38393 analogs, the partial D1 agonist SKF 77434 and the full D1 agonist SKF 82958; both compounds produce inverted U-shaped dose-response curves. When compared to the parent compound, both analogs display enhanced lipophilicity and somewhat decreased D1/D2 selectivity. It is suggested that these properties, rather than partial D1 agonist efficacy, explain the failure of SKF 38393 to act as a reinforcer.
Department of Pharmacology, College of Medicine, University of California, Irvine 92717.
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D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D001552:Benzazepines; D015259:Dopamine Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D012054:Reinforcement, Psychology; D012646:Self Administration
D001552:Benzazepines; D015259:Dopamine Agents; D017447:Receptors, Dopamine D1; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C071262:SK&F 82958; C067114:SK&F 77434