Cross-tolerance between the different mu-opioid receptor agonists endomorphin-1, endomorphin-2 and morphine at the spinal level in the rat.
In the present study we investigated the development of tolerance to an antinociceptive effect after intrathecal administration of endomorphin-1, endomorphin-2 and morphine in tail-flick and paw pressure tests. We also assessed cross-tolerance between the antinociceptive effects of the two endogenous mu-opioid receptor agonists - endomorphins and morphine. The tolerance developed on day 3 after i.th. injection of both endomorphins, endomorphin-2 (18, 36 nmol), endomorphin-1 (16 nmol). After morphine (30 nmol) the tolerance developed on day 6. Our study described the cross-tolerance between morphine and endomorphin-1, but not endomorphin-2. In comparison with naive rats, morphine had a weaker antinociceptive effect in rats tolerant to endomorphin-1. In contrast, no cross-tolerance was observed after administration of endomorphin-2 in rats tolerant to endomorphin-1. In rats tolerant to endomorphin-2, the antinociceptive effect of morphine and endomorphin-1 was attenuated in both the tests used. Our results suggest that the three ligands of mu-opioid receptors probably act via different subtypes of the mu-opioid receptor.
Labuz
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D
Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Kraków, Poland.
Przewlocki
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R
Przewlocka
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B
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004361:Drug Tolerance / Q000502:physiology*; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000187:drug effects
D000701:Analgesics, Opioid; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; C105294:endomorphin 2; D009020:Morphine