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Eur J Pharmacol. 1995 Nov 3;286(1):105-8.

Attenuation of morphine tolerance and dependence with the highly selective delta-opioid receptor antagonist TIPP[psi].

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  • 1Pain Mechanisms Laboratory, Clinical Research Institute of Montreal, Quebec, Canada.


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.

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