PT  - JOURNAL ARTICLE
AU  - J Kamei
AU  - M Ohsawa
AU  - A Saitoh
AU  - Y Iwamoto
AU  - T Suzuki
AU  - M Misawa
AU  - H Nagase
AU  - Y Kasuya
TI  - Modification of mu-opioid agonist-induced locomotor activity and development of morphine dependence by diabetes.
DP  - 1995 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 700--706
VI  - 274
IP  - 2
4099  - http://jpet.aspetjournals.org/content/274/2/700.short
4100  - http://jpet.aspetjournals.org/content/274/2/700.full
SO  - J Pharmacol Exp Ther1995 Aug 01; 274
AB  - We examined the locomotor-enhancing action of mu-opioid receptor agonists, such as morphine and [D-Ala2, N-MePhe4, Gly-ol5]enkephalin (DAMGO), and physical dependence on morphine in diabetic and nondiabetic mice. Morphine (5-20 mg/kg, s.c.) and DAMGO (1-4 nmol, i.c.v.) had a dose-dependent locomotor-enhancing effect in both nondiabetic and diabetic mice. The locomotor-enhancing effects of morphine and DAMGO were significantly less in diabetic mice than in nondiabetic mice, and were significantly reduced after pretreatment with either beta-funaltrexamine (20 mg/kg, s.c.), a selective mu-opioid receptor antagonist, or naloxonazine (35 mg/kg, s.c.), a selective mu1-opioid receptor antagonist. Both diabetic and nondiabetic mice were chronically treated with morphine (8-45 mg/kg, s.c.) for 5 days. During this treatment, neither diabetic nor nondiabetic mice showed any signs of toxicity. After morphine treatment, withdrawal was precipitated by injection of naloxone (0.3-10 mg/kg, s.c.). Several withdrawal signs, such as weight loss, diarrhea, ptosis, jumping and body shakes, were observed after naloxone challenge in morphine-dependent nondiabetic mice. Although morphine-dependent diabetic mice showed greater weight loss than nondiabetic mice, the incidence of jumping and body shakes after naloxone challenge in diabetic mice were lower than that in nondiabetic mice. These results suggest that diabetic mice are selectively hyporesponsive to mu1-opioid receptor-mediated locomotor enhancement. Furthermore, diabetes may affect mu1-opioid receptor-mediated naloxone-precipitated signs of withdrawal from physical dependence on morphine.