Melatonin attenuates the development of antinociceptive tolerance to delta-, but not to mu-opioid receptor agonist in mice.
The effects of melatonin (Mel) on the development of tolerance to antinociceptive actions induced by mu- and delta-opioid receptor agonists were determined in male Kunming mice. In the mouse tail-flick tests, selective mu and delta receptor agonists were repeatedly administered to mice supraspinally (intracerebroventricularly, i.c.v.) in the absence or presence of melatonin. Administration of endomorphin-1 (EM-1, a mu-opioid receptor agonist) or deltorphin I (del I, a delta-opioid receptor agonist) twice daily for 4 days produced antinociceptive tolerance compared with vehicle controls. Co-administration with melatonin prevented the development of tolerance to deltorphin I analgesia, and this effect was dose dependent. However, melatonin did not affect the development of antinociceptive tolerance to endomorphin-1. Additionally, the attenuation of deltorphin I tolerance by melatonin was reduced by chronic treatment with luzindole (luz), a selective antagonist on the MT(2) receptor subtype. Taken together, these data suggest that melatonin interferes with the neural mechanisms involved in the development of tolerance to delta-opioid agonist analgesia via its receptor.
Dai
Xu
X
Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, 222 Tian Shui South Road, Lanzhou 730000, PR China.
Cui
Shi-gang
SG
Li
Shi-rong
SR
Chen
Qiang
Q
Wang
Rui
R
D000701:Analgesics, Opioid / Q000008:administration & dosage; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004361:Drug Tolerance; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D008550:Melatonin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D009842:Oligopeptides / Q000008:administration & dosage; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D017465:Receptors, Opioid, delta / Q000819:agonists*; D014363:Tryptamines / Q000494:pharmacology
D000701:Analgesics, Opioid; D000975:Antioxidants; D004338:Drug Combinations; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D014363:Tryptamines; C105293:endomorphin 1; C057154:luzindole; C059567:deltorphin; D008550:Melatonin