Feeding induced by food deprivation is differentially reduced by opioid receptor antisense oligodeoxynucleotide probes in rats

M. M. Hadjimarkou, E. Khaimova, Y. X. Pan, G. C. Rossi, G. W. Pasternak, R. J. Bodnar

Research output: Contribution to journalArticlepeer-review

Abstract

The increases in food intake following 24 h of food deprivation are reduced by systemic and central administration of general opioid antagonists. The use of selective opioid antagonists revealed that μ-selective antagonists were more effective than κ-selective antagonists in reducing deprivation-induced intake, whereas δ-selective antagonists were minimally effective. Antisense oligodeoxynucleotide (AS ODN) probes directed against different exons of the μ (MOP), δ (DOP), κ (KOP) and nociceptin (NOP) opioid peptide receptor genes have been able to differentially alter feeding responses elicited by glucoprivation, lipoprivation and by different opioid peptides and receptor agonists. The present study examined whether lateral ventricular administration of AS ODN probes directed against different exons of the MOP, DOP, KOP or NOP opioid receptor genes altered food intake and body weight changes following 24 h of food deprivation in rats. Deprivation-induced feeding was significantly and maximally reduced by an AS ODN probe directed against exon 2, but not exons 1 or 3 of the KOP gene. This response was also significantly though modestly reduced by AS ODN probes directed against exons 2, 3 or 4 of the MOP gene, exon 1 of the DOP gene, or exon 1 of the NOP gene. Recovery of body weight following postdeprivation food reintroduction was significantly reduced by AS ODN probes directed against either exons 2, 3 or 4 of the MOP gene, exons 1 or 2 of the DOP gene, or exons 1, 2 or 3 of the KOP gene. The parallel patterns in the magnitude of alterations in deprivation-induced feeding by δ antagonists and DOP AS ODN probes on one hand, and by κ antagonists and KOP AS ODN probes on the other, provide converging and complementary evidence for their relative involvement in this response. The modest reductions by MOP AS ODN probes relative to the more potent reductions induced by μ-selective antagonists suggest that the μ receptor-mediated actions upon deprivation-induced feeding may involve recently-identified splice variants or isoforms of the MOP gene.

Original languageEnglish
Pages (from-to)223-232
Number of pages10
JournalBrain Research
Volume987
Issue number2
DOIs
Publication statusPublished - 17 Oct 2003

Keywords

  • δ-Opioid receptor
  • κ-Opioid receptor
  • μ-Opioid receptor
  • Antisense oligodeoxynucleotide
  • Body weight
  • Food deprivation
  • Food intake

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