title: Lack of antinociceptive cross-tolerance between [D-Pen2, D-Pen5]enkephalin and [D-Ala2]deltorphin II in mice: evidence for delta receptor subtypes.
abstract: This study has investigated the development of antinociceptive tolerance to, and cross-tolerance between, two highly selective delta agonists, [D-Pen2,D-Pen5]enkephalin (DPDPE) and [D-Ala2] deltorphin II as well as to [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAMGO), a highly selective mu agonist, in mice. Intracerebroventricular administration of DPDPE, [D-Ala2]deltorphin II and DAMGO each produced an antinociceptive effect. Pretreatment with i.c.v. DPDPE twice daily for 3 days resulted in tolerance to DPDPE as shown by a 4.8-fold rightward shift in the dose-response curve. In contrast, in DPDPE pretreated mice, the dose-response lines for [D-Ala2]deltorphin II and DAMGO were not altered when compared to those obtained in naive animals. The development of tolerance was also shown by pretreating mice with i.c.v. [D-Ala2]deltorphin II; following this pretreatment, the [D-Ala2]deltorphin II dose-response line was displaced to the right by more than 37-fold. In contrast, in [D-Ala2]deltorphin II-pretreated mice, the dose-response lines for DPDPE and DAMGO were not altered compared to those obtained in naive animals. Finally, pretreatment with i.c.v. DAMGO produced a rightward displacement of the DAMGO dose-response line of 47-fold, indicating the development of antinociceptive tolerance. In DAMGO-pretreated mice, however, the dose-response lines for DPDPE and [D-Ala2]deltorphin II were not altered compared to those obtained in naive mice. Thus, the data indicate that antinociceptive tolerance develops to DPDPE, [D-Ala2]deltorphin II and DAMGO but that there is no cross-tolerance between these compounds.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, University of Arizona Health Sciences Center, Tucson.
authors.forename: A
authors.initials: A
authors.lastname: Mattia
authors.forename: T
authors.initials: T
authors.lastname: Vanderah
authors.forename: H I
authors.initials: HI
authors.lastname: Mosberg
authors.forename: F
authors.initials: F
authors.lastname: Porreca
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004361:Drug Tolerance; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009842:Oligopeptides / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000032:analysis / Q000187:drug effects*; D017465:Receptors, Opioid, delta
chemical_list: D000700:Analgesics; D004745:Enkephalins; D009842:Oligopeptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C060209:deltorphin II, Ala(2)-; D020881:Enkephalin, D-Penicillamine (2,5)-