SEX DIFFERENCES IN THE REDUCTION OF HOPELESSNESS IN Μ OPIOID RECEPTOR DEFICIENT MICE BY ADDITIVE EFFECTS OF Δ OPIOID RECEPTOR AGONISTS

Abstract Previous pharmacological data have shown the possible existence of functional interactions between μ, κ, and δ opioid receptors in pain and mood disorders. We have reported previously μ opioid receptor knockout (MOP-KO) mice showed a reduced stress responses compared to the wild type (WT) mice. Moreover, δ opioid receptor (DOP) agonists have been shown to affect antidepressant-like effects in a number of animal models. The tail suspension test (TST) and the forced swim test (FST) were used to examine the roles of MOP and DOP in hopeless emotional effects MOP-KO mice and WT mice were treated with KNT-127, a selective DOP agonist. The results indicated that there was a significant decrease in immobility time in the KNT-127 group compared to the saline group in all genotypes in both tests. In the saline groups, immobility time was significantly decreased in MOP-KO mice compared to WT mice in both tests. In female MOP-KO mice, the results showed that KNT-127 significantly decreased immobility time compared to the WT mice in TST. In male MOP-KO mice, however, TST showed that the KNT-127 or the saline treated do not reduced immobility time for genotype comparisons. Thus, at least in FST and TST, activation of DOP and absence of MOP had additive effects on reducing the hopelessness, suggesting that the lack of motivated behavior by activation of DOP functions independently of MOP.