Abstract
Effects of highly selective δ-opioid receptor antagonists on the morphine-induced place preference in ddY and μ1-opioid receptor deficient CXBK mice were investigated. Pretreatment with naltrindole (NTI: a non-selective δ-opioid receptor antagonist), 7-benzylidenenaltrexone (BNTX: a selective δ1-opioid receptor antagonist) or naltriben (NTB: a selective δ2-opioid receptor antagonist) abolished the morphine-induced place preference in ddY mice in a dose-dependent manner. These findings suggest that the morphine-induced place preference may be mediated by both δ1 and δ2-opioid receptors. On the other hand, in μ1-opioid receptor deficient CXBK mice, pretreatment with these selective δ-opioid receptor antagonists did not affect the morphine-induced place preference, although pretreatment with β-funaltrexamine (β-FNA: a selective μ-opioid receptor antagonist) significantly inhibited the morphine-induced place preference. [D-Pen2, D-Pen5]enkephalin (DPDPE: a δ1-opioid receptor agonist) and [D-Ala2, Glu4]deltorphin (deltorphin II: a δ2-opioid receptor agonist) induced a significant place preference in ddY mice, but not in CXBK mice. These results suggest that δ1- and δ2-opioid receptors in the nucleus accumbens that are related to the DPDPE- and deltorphin II-induced place preference may be dysfunctional and/or poor in CXBK mice. These findings also indicate that δ1- and δ2-opioid receptors may be involved in the modulation of the reinforcing effect of morphine.
