Attenuation of morphine tolerance and dependence with the highly selective delta-opioid receptor antagonist TIPP[psi].
We examined the effects of i.c.v. treatment with naltrindole, and the two highly selective peptide delta-opioid receptor antagonists H-Tyr-Tic-Phe-Phe-OH (TIPP) and H-Tyr-Tic psi [CH2-NH]-Phe-Phe- OH (TIPP[psi]), on the development of morphine tolerance and dependence. Each treatment significantly decreased naloxone-precipitated withdrawal, with TIPP[psi] reducing the most symptoms. TIPP[psi], but neither naltrindole nor TIPP, attenuated the development of analgesic tolerance in the tail-flick test. These results suggest that delta-opioid receptors are critically involved in the development of morphine tolerance and dependence.
Fundytus
M E
ME
Pain Mechanisms Laboratory, Clinical Research Institute of Montreal, Quebec, Canada.
Schiller
P W
PW
Shapiro
M
M
Weltrowska
G
G
Coderre
T J
TJ
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D009021:Morphine Dependence / Q000503:physiopathology*; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D044005:Tetrahydroisoquinolines
D009292:Narcotic Antagonists; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D044005:Tetrahydroisoquinolines; C092721:tyrosyl-tetrahydroisoquinolinecarbonyl-psi(methylamino)phenylalanyl-phenylalanine; C082263:tyrosyl-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-phenylalanyl-phenylalanine; D009270:Naloxone; D009271:Naltrexone; C055382:naltrindole