The effects of dopamine D1 and D2 receptor antagonists on the rewarding effects of delta 1 and delta 2 opioid receptor agonists in mice.

The effects of the dopamine D1 antagonist SCH23390 and the D2 antagonist sulpiride on the rewarding effects of delta opioid receptor agonists were examined in mice. Both [D-Pen2, Pen5]enkephalin (DPDPE, 1-15 nmol, ICV), a selective delta 1 opioid receptor agonist, and [D-Ala2]deltorphin II (DELT, 0.5-5 nmol, ICV), a selective delta 2 opioid receptor agonist, produced a dose-dependent place preference in mice. The DPDPE (15 nmol, ICV)-induced place preference was abolished by BNTX (0.5 mg/kg, SC), a delta 1 opioid receptor antagonist, but not by NTB (0.5 mg/kg, SC), a delta 2 opioid receptor antagonist. In contrast, the DELT (5 nmol, ICV)-induced place preference was antagonized by NTB, but not BNTX. Pretreatment with SCH23390 (3 micrograms/kg, SC) abolished the DPDPE-induced place preference, but not affect the DELT-induced place preference. Moreover, pretreatment with sulpiride (40 mg/kg, SC) did not modify the place preference induced by DPDPE or DELT. In the present study, we found that the activation of both central delta 1 and delta 2 opioid receptors produced rewarding effects. Furthermore, these results suggest that the rewarding effects of delta 1 opioid receptor agonist may be produced through activation of the central dopaminergic system, especially dopamine D1 receptors, whereas the rewarding effects of delta 2 opioid receptor agonists may be produced by some other mechanism(s).