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Acute naloxone-precipitated morphine withdrawal elicits nausea-like somatic behaviors in rats in a manner suppressed by N-oleoylglycine.

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  • Additional Information
    • Source:
      Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 7608025 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-2072 (Electronic) Linking ISSN: 00333158 NLM ISO Abbreviation: Psychopharmacology (Berl) Subsets: MEDLINE
    • Publication Information:
      Original Publication: Berlin, New York, Springer-Verlag.
    • Subject Terms:
      Glycine/*analogs & derivatives ; Morphine/*adverse effects ; Naloxone/*toxicity ; Narcotic Antagonists/*toxicity ; Nausea/*drug therapy ; Oleic Acids/*therapeutic use ; Substance Withdrawal Syndrome/*drug therapy; Animals ; Female ; Glycine/pharmacology ; Glycine/therapeutic use ; Male ; Medically Unexplained Symptoms ; Morphine Dependence/drug therapy ; Morphine Dependence/physiopathology ; Nausea/chemically induced ; Nausea/physiopathology ; Oleic Acids/pharmacology ; Rats ; Rats, Sprague-Dawley ; Shrews ; Substance Withdrawal Syndrome/etiology ; Substance Withdrawal Syndrome/physiopathology
    • Abstract:
      Rationale: Acute naloxone-precipitated morphine withdrawal (MWD) produces a conditioned place aversion (CPA) in rats even after one or two exposures to high-dose (20 mg/kg, sc) morphine followed 24-h later by naloxone (1 mg/kg, sc). However, the somatic withdrawal reactions produced by acute naloxone-precipitated MWD in rats have not been investigated. A recently discovered fatty acid amide, N-oleoylglycine (OlGly), which has been suggested to act as a fatty acid amide hydrolase (FAAH) inhibitor and as a peroxisome proliferator-activated receptor alpha (PPARα) agonist, was previously shown to interfere with a naloxone-precipitated MWD-induced CPA in rats.
      Objectives: The aims of these studies were to examine the somatic withdrawal responses produced by acute naloxone-precipitated MWD and determine whether OlGly can also interfere with these responses.
      Results: Here, we report that following two exposures to morphine (20 mg/kg, sc) each followed by naloxone (1 mg/kg, sc) 24 h later, rats display nausea-like somatic reactions of lying flattened on belly, abdominal contractions and diarrhea, and display increased mouthing movements and loss of body weight. OlGly (5 mg/kg, ip) interfered with naloxone-precipitated MWD-induced abdominal contractions, lying on belly, diarrhea and mouthing movements in male Sprague-Dawley rats, by both a cannabinoid 1 (CB 1 ) and a PPARα mechanism of action. Since these withdrawal reactions are symptomatic of nausea, we evaluated the potential of OlGly to interfere with lithium chloride (LiCl)-induced and MWD-induced conditioned gaping in rats, a selective measure of nausea; the suppression of MWD-induced gaping reactions by OlGly was both CB 1 and PPARα mediated.
      Conclusion: These results suggest that the aversive effects of acute naloxone-precipitated MWD reflect nausea, which is suppressed by OlGly.
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    • Grant Information:
      03629 Natural Sciences and Engineering Research Council of Canada; 388239 Institute of Neurosciences, Mental Health and Addiction
    • Contributed Indexing:
      Keywords: Acute naloxone-precipitated morphine withdrawal; CB1; Gaping; N-oleoylglycine; Nausea; PPARα; Rats; Somatic MWD
    • Accession Number:
      0 (N-oleoylglycine)
      0 (Narcotic Antagonists)
      0 (Oleic Acids)
      36B82AMQ7N (Naloxone)
      76I7G6D29C (Morphine)
      TE7660XO1C (Glycine)
    • Publication Date:
      Date Created: 20191113 Date Completed: 20200804 Latest Revision: 20200804
    • Publication Date:
      20231215
    • Accession Number:
      10.1007/s00213-019-05373-2
    • Accession Number:
      31712968