title: Acute antinociceptive tolerance and unidirectional cross-tolerance to endomorphin-1 and endomorphin-2 given intraventricularly in the rat.
abstract: The effect of the pretreatment with endomorphin-1 or endomorphin-2 given into anterior 4th ventricle (i.vt.) on the antinociception with the tail-flick test induced by subsequent intraventricular (i.vt.) injection of endomorphin-1 or endomorphin-2 were studied in rats. The i.vt. pretreatment with 30 nmol of endomorphin-1 or 60 nmol of endomorphin-2 developed an antinociceptive tolerance to the subsequently challenging dose of i.vt.-administered endomorphin-1 or endomorphin-2, respectively, with different time courses. The endomorphin-1-induced antinociceptive tolerance reached a maximal level at 2 h, recovered slowly in 24 h after the pretreatment with endomorphin-1, whereas endomorphin-2-induced antinociceptive tolerance developed in 1 h and recovered in 4 h. Rats made tolerant to endomorphin-1 by i.vt. pretreatment with endomorphin-1 exhibited nearly no cross-tolerance to endomorphin-2 to produce antinociception. On the other hand, rats made tolerant to endomorphin-2 exhibited a complete cross-tolerance to endomorphin-1 to produce antinociception. We propose that different degrees of receptor endocytosis for receptor inactivation after stimulation of mu-opioid receptors by endomorphin-1 and endomorphin-2 and/or two separate subtypes of mu-opioid receptors are involved in the antinociception induced by endomorphin-1 and endomorphin-2.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, MEB-M4308, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
authors.forename: Kuei-chun
authors.initials: KC
authors.lastname: Hung
authors.forename: Hsiang-en
authors.initials: HE
authors.lastname: Wu
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Mizoguchi
authors.forename: Leon F
authors.initials: LF
authors.lastname: Tseng
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D051381:Rats; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000502:physiology
chemical_list: D000700:Analgesics; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; C105294:endomorphin 2