Abstract
We examined the effects of i.c.v. treatment with naltrindole, and the two highly selective peptide δ-opioid receptor antagonists H-Tyr-Tic-Phe-Phe-OH (TIPP) and H-Tyr-Ticψ[CH 2-NH]-Phe-Phe-OH (TIPP[ψ]), on the development of morphine tolerance and dependence. Each treatment significantly decreased naloxone-precipitated withdrawal, with TIPP[ψ] reducing the most symptoms. TIPP[ψ], but neither naltrindole nor TIPP, attenuated the development of analgesic tolerance in the tail-flick test. These results suggest that δ-opioid receptors are critically involved in the development of morphine tolerance and dependence.
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