title: Tolerance and dependence following chronic intracerebroventricular infusions of Tyr-D-Arg2-Phe-Sar4 (TAPS).
abstract: The dermorphin-derived tetrapeptide Tyr-D-Arg(2)-Phe-Sar(4) (TAPS) was tested for its ability to induce tolerance, cross-tolerance, withdrawal and its substitution properties in rats subjected to chronic intracerebroventricular (i.c.v.) infusions of mu-opiate receptor agonists. Tolerance and cross-tolerance were assessed by quantification of the thermally induced tail-flick response. Chronic intracerebroventricular infusion of TAPS resulted in antinociception at almost 1000-fold lower doses compared to morphine sulphate and [D-Ala(2), MePhe(4)Gly(ol)(5)]enkephalin (DAMGO). Tolerance to the antinociceptive effect of TAPS developed similar to DAMGO and morphine sulphate. Cross-tolerance to intracerebroventricular bolus injections of DAMGO, but not of TAPS, was evident in rats rendered tolerant to morphine sulphate and TAPS. Naloxone-induced withdrawal was equally pronounced in animals treated with morphine sulphate, DAMGO or TAPS. TAPS substituted for morphine sulphate and vice versa regarding the withdrawal syndrome in a cross-over experimental design. In contrast to DAMGO, TAPS retains its antinociceptive effect following bolus administration in rats rendered tolerant to mu-opioid receptor agonists.
authors.affiliation: Department of Cardiology and Pneumology, Georg-August-University, Robert-Koch-Str. 40, 37075, Göttingen, Germany. svonhof@gwdg.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Vonhof
authors.forename: Bijal D
authors.initials: BD
authors.lastname: Gudka
authors.forename: Anna Leena
authors.initials: AL
authors.lastname: Sirén
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D066298:In Vitro Techniques; D007260:Infusion Pumps; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000008:administration & dosage; D009842:Oligopeptides / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D019966:Substance-Related Disorders; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D009842:Oligopeptides; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D009020:Morphine; C053418:tyrosyl-arginyl-phenylalanyl-sarcosine