Motivational effects of opioids: influence of D-1 versus D-2 receptor antagonists.
An unbiased place preference conditioning procedure was used to: (i) characterize the motivational effects of dopamine (DA)-receptor antagonists and (ii) examine the role of D-1 versus D-2 DA receptors in mediating the reinforcing and aversive properties of opioids. Acute administration of the D-1 antagonist, SCH 23390 (0.001-0.5 mg/kg), produced conditioned place aversions. In contrast, the D-2 antagonists, (-)-sulpiride and spiperone, were motivationally neutral, lacking reinforcing or aversive effects. Chronic infusion of SCH 23390 (1.0 mg/kg per day) during the conditioning sessions abolished the reinforcing effect of the mu-opioid agonist, morphine, and the place aversions produced by the kappa-opioid agonist, U-69593, and the opioid antagonist, naloxone. D-2 antagonists were ineffective in modifying the motivational properties of opioid agonists and naloxone. These data demonstrate the involvement of D-1 but not D-2 receptors in the motivational properties of opioids and suggest that the D-1 receptor is critical for the expression of reinforcing and aversive motivational states.
Shippenberg
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Department of Neuropharmacology, Max-Planck-Institut für Psychiatrie, Planegg-Martinsried, F.R.G.
Herz
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D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D044482:Benzeneacetamides; D003213:Conditioning, Psychological; D008094:Lithium / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009042:Motivation / Q000187:drug effects* / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000502:physiology; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D012054:Reinforcement, Psychology
D001552:Benzazepines; D044482:Benzeneacetamides; D011759:Pyrrolidines; D011954:Receptors, Dopamine; D011957:Receptors, Opioid; D009270:Naloxone; D009020:Morphine; D008094:Lithium; C045444:U 69593