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-T ic-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 treatme nt significantly decreased naloxone-precipitated withdrawal, with TIPP [psi] reducing the most symptoms. TIPP[psi], but neither naltrindole n or TIPP, attenuated the development of analgesic tolerance in the tail -flick test. These results suggest that delta-opioid receptors are cri tically involved in the development of morphine tolerance and dependen ce.