Involvement of dopamine-dependent and -independent mechanisms in the rewarding effects mediated by δ opioid receptor subtypes in mice

Abstract

The rewarding effects of the δ 1 opioid receptor agonist [D-Pen 2, Pen 5]enkephalin (DPDPE) and the δ 2 opioid receptor agonist [D-Ala 2]deltorphin II (DELT) on the activity of mesolimbic and nigrostriatal dopamine (DA) neurons were examined in mice. Both DPDPE (15 nmol, i.c.v.) and DELT (5 nmol, i.c.v.) produced a significant place preference in mice. The DPDPE (15 nmol, i.c.v.)-induced place preference was abolished by 7-benzylidenenaltrexone (BNTX; 0.5 mg/kg, s.c.), a δ 1 opioid receptor antagonist, but not by naltriben (NTB; 0.5 mg/kg, s.c.), a δ 2 opioid receptor antagonist. In contrast, the DELT (5 nmol, i.c.v.)-induced place preference was antagonized by NTB, but not BNTX. I.c.v. injection of DPDPE, but not DELT, at a dose that produced a significant place preference produced a significant elevation of DA turnover in the mouse limbic forebrain, and this effect of DPDPE was antagonized by BNTX but not by NTB. In addition, i.c.v. injection of DPDPE or DELT did not affect DA turnover in the mouse striatum. These results suggest that the rewarding effects produced by the activation of central δ 1, but not δ 2, opioid receptors may be caused through the enhancement of the mesolimbic DA neurotransmission, and confirm our previous hypothesis that the DA-dependent and -independent mechanisms may exist in the rewarding effects produced by the activation of central δ opioid receptor subtypes.