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Differential sensitivity of opioid-induced feeding to naloxone and naloxonazine

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Abstract

The high-affinity mu-1 opioid binding site has been implicated in some opioid responses (e.g., supraspinal analgesia) but not others (e.g., respiratory depression) by comparing the actions of naloxone, a short-acting, non-selective antagonist, and naloxonazine, an irreversible and selective mu-1 antagonist. The mu-1 site has been implicated in the opioid component modulating free feeding and deprivation-induced feeding, but not glucoprivic feeding. The present study compared naloxone and naloxonazine antagonism of hyperphagia induced by morphine, ethylketocyclazocine (EKC), dynorphin and d-ala2,d-leu5-enkephalin (DADL) in rats. Morphine produced a dose-dependent (0.01–5 mg/kg) hyperphagia in midly food-deprived rats that was blocked by naloxone (0.01–10 mg/kg). Naloxonazine (10 mg/kg) shifted the morphine hyperphagia dose-response curve to the right. These effects could not be fully accounted for by the intrinsic hypophagic properties of these antagonists. EKC produced a dose-dependent (0.5–5 mg/kg) hyperphagia which was blocked by naloxone (10 mg/kg) only at low effective EKC doses. Naloxonazine (10 mg/kg) failed to affect EKC hyperphagia. Naloxone, but not naloxonazine also blocked dynorphin and DADL hyperphagia. These results indicate that feeding induced by opiate and opioid agonists are differentially mediated by the mu-1 and other opioid binding sites; these data contrast with the modulation by the mu-1 site of the supraspinal analgesia induced by each of these agonists.

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Author notes

  1. Phyllis E. Mann

    Present address: Department of Anatomy and Cellular Biology, Harvard Medical School/LHRRB, USA

  2. Maria-Teresa Romero

    Present address: Department of Psychology, Barnard College, Columbia University, USA

Authors and Affiliations

  1. Department of Psychology and Neuropsychology Doctoral Sub-Program, Queens College, CUNY, 11367, Flushing, NY, USA

    Phyllis E. Mann, Dulmanie Arjune, Maria-Teresa Romero & Richard J. Bodnar

  2. The George C. Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, and Departments of Neurology and Pharmacology, Cornell University Medical College, 10021, New York, NY, USA

    Gavril W. Pasternak

  3. Laboratory of Biochemical Endocrinology, Rockefeller University, 10021, New York, NY, USA

    Elliot F. Hahn

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  1. Phyllis E. Mann
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  2. Dulmanie Arjune
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  4. Gavril W. Pasternak
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  5. Elliot F. Hahn
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  6. Richard J. Bodnar
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Mann, P.E., Arjune, D., Romero, MT. et al. Differential sensitivity of opioid-induced feeding to naloxone and naloxonazine. Psychopharmacology 94, 336–341 (1988). https://doi.org/10.1007/BF00174686

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  • DOI: https://doi.org/10.1007/BF00174686

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