The effect of chronic treatment with naltrindole, a selective delta-opioid antagonist, on mu-opioid receptor-mediated antinociception in diabetic mice.
The effects of chronic treatment with naltrindole (NTI), a selective delta-opioid receptor antagonist, on the antinociceptive effects of mu-opioid agonists, such as morphine and [D-Ala2, N-MePhe4, Gly-ol(5)]enkephalin (DAMGO) were examined in diabetic mice. Antinociception induced by morphine (10 micrograms, ICV) and DAMGO (0.5 microgram, ICV) was significantly lower in diabetic mice than in non-diabetic mice. The low sensitivities to the antinociceptive potencies of ICV morphine (10 micrograms) and DAMGO (0.5 micrograms) in diabetic mice were reversed compared with those in saline-treated non-diabetic mice when diabetic mice had been pretreated with NTI (2 mg/kg per day, SC) for 14 days. Naive mice which had been injected with spleen mononuclear cells from saline-treated diabetic mice were less sensitive to DAMGO-induced antinociception. However, adoptive transfer of spleen mononuclear cells from NTI-treated diabetic mice to naive mice had no effect on the recipients' antinociceptive sensitivity to DAMGO. These results suggest that the effect of NTI on the sensitivity to mu-opioid agonists in diabetic mice may be due to the immunosuppressive effects of NTI.
Department of Pharmacology, Faculty of Pharmaceutical Science, Hoshi University, Tokyo, Japan.
J
J
Kamei
N
N
Kawashima
Y
Y
Iwamoto
T
T
Suzuki
H
H
Nagase
M
M
Misawa
Y
Y
Kasuya
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000523:psychology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D013154:Spleen / Q000166:cytology
D000700:Analgesics; D004745:Enkephalins; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009271:Naltrexone; D009020:Morphine; C055382:naltrindole