tyrosyl-1-2-3-4-tetrahydro-3-isoquinolinecarbonyl-phenylalanyl-phenylalanine and Substance-Withdrawal-Syndrome

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.

Topics: Animals; Behavior, Animal; Morphine Dependence; Naloxone; Naltrexone; Narcotic Antagonists; Oligopeptides; Rats; Receptors, Opioid, delta; Substance Withdrawal Syndrome; Tetrahydroisoquinolines