Supraspinal delta receptor subtype activity of heroin and 6-monoacetylmorphine in Swiss webster mice

Jodie J. Rady, A. E. Takemori, P. S. Portoghese, James M. Fujimoto

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26 Scopus citations

Abstract

The purpose of this study was to determine which delta (δ) opioid receptor subtype, δ1 or δ2, was involved in producing the antinociceptive action of heroin and 6-monacetylmorphine (MAM) in Swiss Webster mice. Previous work from this laboratory established that heroin and MAM, given intracerebroventricularly (i.c.v.) in Swiss Webster mice, produce antinociception through activation of supraspinal δ receptors. Naltrindole, but not naloxone or nor-binaltorphimine, antagonizes the inhibitory action of heroin and MAM in the tail-flick test. Recent literature documents the occurence of subtypes of the δ opioid receptor and the availability of selective antagonists. 7-Benzylidenenaltrexone (BNTX) antagonizes the antinociception induced by δ1 receptor agonists without affectingthat induced by δ2 receptor agonists. Naltriben (NTB) selectively inhibits δ2- but not δ1-induced antinociception. In the present study BNTX and NTB were administered i.c.v. with heroin and MAM to determine the δ receptor subtype responsible for inhibition of the tail-flick response in Swiss Webster mice. The ED50 for heroin-induced antinociception was increased 19-fold by BNTX and was not altered by NTB administration. On the other hand, the ED50 value of MAM was increased 3-fold by NTB and was not altered b by BNTX administration. These results suggest that heroin activated supraspinal δ1 receptors and MAM acted on supraspinal δ2 receptors to produce antinociception in Swiss Webster mice.

Original languageEnglish (US)
Pages (from-to)603-609
Number of pages7
JournalLife Sciences
Volume55
Issue number8
DOIs
StatePublished - 1994

Bibliographical note

Funding Information:
This work was supportedb y Grant DA00451 from the National Instituteo n Drug Abuse and Veteran AdministrationM edical Research Funds (Research Career Scientist Award).

Keywords

  • 6-monoacetylmorphine
  • delta subtype
  • heroin
  • δ opioid receptors

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