10945849

pubmed:Citation

3

delta-Opioid receptors have been implicated in reinforcement processes and antagonists are available that produce long-lasting and selective antagonism of delta-opioid receptors in vivo. This experiment assessed the contribution of delta-opioid receptors to the antinociceptive and reinforcing properties of heroin. The effects of the irreversible delta-antagonist naltrindole-5'-isothiocyanate (5'-NTII) were evaluated on heroin self-administration and hot-plate antinociception in rats. 5'-NTII (10 nmol i.c.v.) shifted the dose-response curve for heroin self-administration downward, increasing the A(50) values on the ascending and descending limbs by approximately 0.5 log units and decreasing the maximum by 33%. 5'-NTII (40 nmol i.c.v.) shifted both limbs of the heroin self-administration dose-effect curve 1.2 log units to the right and decreased the maximum by 90%. Heroin self-administration gradually returned to baseline levels over 7 or 17 days after administration of 10 or 40 nmol 5'-NTII, respectively. 5'-NTII (40 nmol i.c.v.) decreased the self-administration of 0.17 mg/infusion cocaine by 40% while having no effect on responding maintained by 0.33 or 0.67 mg/infusion. 5'-NTII attenuated the antinociceptive effects of deltorphin (delta(2)) in a dose-dependent manner while having no effect on antinociception elicited after i.c. v. administration of [D-Pen(2),D-Pen(5)]-enkephalin (delta(1)) or [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (mu). In addition, the antinociceptive effects of heroin were not significantly affected by 5'-NTII (40 nmol i.c.v.). Therefore, 5'-NTII can attenuate the reinforcing effects of heroin at doses that do not affect its antinociceptive effects. Long-acting delta(2)-opioid antagonists may be beneficial in the treatment of heroin dependence or as adjuncts to reduce the abuse liability of opioid analgesics.

eng

IM

MEDLINE

0022-3565

Print

NLM

975-82

pubmed-meshheading:10945849-Analgesics, Opioid, pubmed-meshheading:10945849-Animals, pubmed-meshheading:10945849-Cocaine, pubmed-meshheading:10945849-Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, pubmed-meshheading:10945849-Enkephalin, D-Penicillamine (2,5)-, pubmed-meshheading:10945849-Heroin, pubmed-meshheading:10945849-Injections, Intraventricular, pubmed-meshheading:10945849-Isothiocyanates, pubmed-meshheading:10945849-Male, pubmed-meshheading:10945849-Naltrexone, pubmed-meshheading:10945849-Narcotic Antagonists, pubmed-meshheading:10945849-Oligopeptides, pubmed-meshheading:10945849-Pain Measurement, pubmed-meshheading:10945849-Rats, pubmed-meshheading:10945849-Rats, Inbred F344, pubmed-meshheading:10945849-Receptors, Opioid, delta, pubmed-meshheading:10945849-Reinforcement (Psychology), pubmed-meshheading:10945849-Self Administration

Antagonism of delta(2)-opioid receptors by naltrindole-5'-isothiocyanate attenuates heroin self-administration but not antinociception in rats.

Journal Article, Research Support, U.S. Gov't, P.H.S.