Modification of morphine-induced place preference by diabetes

Abstract

The effects of diabetes on morphine-induced place preference in mice were examined. Morphine caused dose-related place preference in both diabetic and non-diabetic mice. This morphine-induced place preference in diabetic mice was greater than that in non-diabetic mice. The morphine (5 mg/kg)-induced place preference in both diabetic and non-diabetic mice was significantly antagonized by pretreatment with β-funaltrexamine, a selective μ-opioid receptor antagonist, but not with naloxonazine, a selective μ 1-opioid receptor antagonist. The morphine (5 mg/kg)-induced place preference in non-diabetic mice was attenuated by pretreatment with either naltriben, a selective δ 2-opioid receptor antagonist, or 7-benzylidenenaltrexone, a selective δ 1-opioid receptor antagonist. Moreover, the morphine (10 mg/kg)-induced place preference in non-diabetic mice was antagonized by pretreatment with 7-benzylidenenaltrexone (0.7 mg/kg). Although 7-benzylidenenaltrexone had no effect on the place preference induced by 5 mg/kg morphine in diabetic mice, it reduced the place preference induced by 3 mg/kg morphine. Furthermore, the morphine (5 mg/kg)-induced place preference in diabetic mice was significantly antagonized by co-pretreatment with β-funaltrexamine (10 mg/kg) and 7-benzylidenenaltrexone (0.7 mg/kg). 2-Methyl-4a α-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12a α-octahydroquinolino[2,3,3-g]isoquinoline (TAN-67), a non-peptide δ-opioid receptor agonist, produced place preference in diabetic, but not in non-diabetic mice. These results support the hypothesis that the morphine-induced place preference is mainly mediated through the activation of the μ 2-opioid receptor. Furthermore, the enhancement of the morphine-induced place preference in diabetic mice may be due to the up-regulation of δ-opioid receptor-mediated functions.