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.