Modification of morphine-induced place preference by diabetes.
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 beta-funaltrexamine, a selective mu-opioid receptor antagonist, but not with naloxonazine, a selective mu1-opioid receptor antagonist. The morphine (5 mg/kg)-induced place preference in non-diabetic mice was attenuated by pretreatment with either naltriben, a selective delta2-opioid receptor antagonist, or 7-benzylidenenaltrexone. a selective delta1-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 beta-funaltrexamine (10 mg/kg) and 7-benzylidenenaltrexone (0.7 mg/kg). 2-Methyl-4a alpha-(3-hydroxyphenyl)- 1,2,3,4,4a,5,12,12a alpha-octahydroquinolino[2,3,3-g]isoquinoline (TAN-67), a non-peptide delta-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 mu2-opioid receptor. Furthermore, the enhancement of the morphine-induced place preference in diabetic mice may be due to the up-regulation of delta-opioid receptor-mediated functions.
Kamei
J
J
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Ohsawa
M
M
Suzuki
T
T
Nagase
H
H
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D012054:Reinforcement, Psychology; D015854:Up-Regulation
D009294:Narcotics; D011804:Quinolines; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C094142:TAN 67; D009020:Morphine