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Aversive properties of naloxone in non-dependent (naive) rats may involve blockade of central β-endorphin

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Abstract

The present study examines the influence of destruction of the medio-basal arcuate hypothalamus (MBH), the primary site of synthesis of central pools of β-endorphin (β-EP), upon the aversive properties of naloxone in a conditioned place preference paradigm. Bilateral radiofrequency lesions of the MBH resulted in a pronounced fall in levels of immunoreactive β-EP in the brain. Lesioned rats, in contrast to non-operated animals, showed a clear reduction in the conditioned place aversion produced by naloxone. However, they showed no loss of the conditioned preference produced by the mu-selective opioid receptor agonist, morphine, or the conditioned aversion produced by the kappaselective agonist, U50-488. In contrast to the effect of the lesions, suppression of circulating β-EP by dexamethasone treatment failed to influence conditioning produced by naloxone. Thus, the data indicate that the aversive properties of naloxone are attenuated by disruption of central (but not peripheral) β-EP activity. We suggest that these properties of naloxone reflect an antagonism of β-EP activity in the brain. In addition, the data indicate that differing mechanisms underlie the aversive actions of naloxone as compared to U50-488.

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References

  • Bechara A, van der Kooy D (1984) Endogenous opioids: opposite motivational effects in brain and periphery. Neurosci Soc Abst 10:312

    Google Scholar 

  • Chavkin C, James IF, Goldstein A (1982) Dynorphin is a specific endogenous ligand of the κ opioid receptor. Science 215:413–415

    Google Scholar 

  • Downs DA, Woods JA (1976) Naloxone as a negative reinforcer in rhesus monkeys: effect of dose, schedule, and narcotic regimen. Pharmacol Rev 27:397–436

    Google Scholar 

  • Dum J, Gramsch C, Herz A (1983) Activation of hypothalamic β-endorphin pools by reward induced by highly palatable food. Pharmacol Biochem Behav 18:443–457

    Google Scholar 

  • Finley JCW, Lindström P, Petrusc P (1981) Immunocytochemical localization of β-endorphin-containing neurons in the rat brain. Neuroendocrinology 33:28–42

    Google Scholar 

  • Gillan MGC, Kosterlitz HW, Magnan J (1981) Unexpected antagonism in the rat vas deferens by benzomorphans which are agonist in other pharmacological tests. Br J Pharmacol 72:13–15

    Google Scholar 

  • Goldberg SR, Hoffmeister F, Schlichting V, Wuttke W (1971) Aversive properties of nalorphine and naloxone in morphine-dependent monkeys. J Pharmacol Exp Ther 179:268–276

    Google Scholar 

  • Guillemin R, Vargo T, Rossier J, Minick S, Ling N, Rivier C, Vale W, Bloom F (1977) β-endorphin and adrenocorticotropin are secreted concomitantly by the pituitary gland. Science 197:1367–1369

    Google Scholar 

  • Han JS, Xie GX (1984) Dynorphin: important mediator for electroacupuncture in the spinal cord of the rabbit. Pain 18:367–376

    Google Scholar 

  • Höllt V (1983) Multiple endogenous opioid peptides. Trends Neurosci 6:24–26

    Google Scholar 

  • Höllt V, Haarmann I, Seizinger BR, Herz A (1981) Levels of dynorphin (1–13) immunoreactivity in rat neurointermediate pituitaries are concomitantly altered with those of leucine-enkephalin and vasopressin in response to various endocrine manipulations. Neuroendocrinology 33:333–339

    Google Scholar 

  • Huidobro-Tori JP, Way EL (1979) Studies on the hypothermic response of β-endorphin in mice. J Pharmacol Exp Ther 211:50–58

    Google Scholar 

  • König JFR, Klippel RA (1963) The rat brain (a stereotaxic atlas). Williams and Wilkins, Baltimore

    Google Scholar 

  • Kosterlitz HW, Watt AJ (1968) Kinetic parameters of narcotic agonists and antagonists, with particular reference to N-allylnoroxymorphone (naloxone). Br J Pharmacol 33:266–276

    Google Scholar 

  • Millan MH, Millan MJ, Przewlocki R (1984) Lesions of the hypothalamic arcuate nucleus modify discrete brain and pituitary pools of dynorphin in addition to β-endorphin in the rat. Neurosci Lett 48:149–154

    Google Scholar 

  • Millan MJ, Gramsch C, Przewłocki R, Höllt V, Herz A (1980) Lesions of the hypothalamic arcuate nucleus produce a temporary hyperalgesia and attenuate stress-evoked analgesia. Life Sci 27:1513–1523

    Google Scholar 

  • Mogenson GJ, Jones DL, Yim CY (1980) From motivation to action: functional interface between the limbic system and the motor system. Prog Neurobiol 14:69–97

    Google Scholar 

  • Mucha RF, Herz A (1985) Motivational properties of kappa and mu opioid receptor agonists studied with place and taste preference conditioning. Psychopharmacology (in press)

  • Mucha RF, Iversen LL (1984) Reinforcing properties of morphine and naloxone revealed by conditioned place preferences, a procedural examination. Psychopharmacology 82:244–247

    Google Scholar 

  • Mucha RF, van der Kooy D, O'Shaughnessy M, Bucenieks P (1982) Drug reinforcement studied by use of place conditioning in rat. Brain Res 243:91–105

    Google Scholar 

  • Olney JW, Rhee V, de Gubarett T (1977) Neurotoxic effects of glutamate on mouse area postrema. Brain Res 120:151–157

    Google Scholar 

  • Petrillo P, Gambino MC, Tavani A (1984) Bremazocine induces antinociception, but prevents opioid-induced constipation and catatonia in rats and precipitates withdrawal in morphine-dependent rats. Life Sci 35:917–927

    Google Scholar 

  • Phillips AG, LePiane FG (1980) Reinforcing effects of morphine microinjection into the ventral tegmental area. Pharmacol Biochem Behav 12:965–968

    Google Scholar 

  • Robson LE, Paterson SJ, Kosterlitz HW (1983) Opiate receptors. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology Vol 17, Plenum Press, New York, pp 13–80

    Google Scholar 

  • Stolerman I, Pilcher CW, D'Mello GD (1978) Stereospecific aversive property of narcotic antagonists in morphine-free rats. Life Sci 22:1755–1762

    Google Scholar 

  • van der Kooy D, Mucha RF, O'Shaughnessy M, Bucenieks P (1982) Reinforcing effects of brain microinjections of morphine revcaled by conditioned place preference. Brain Res 243:107–117

    Google Scholar 

  • van Ree JM, Smyth DG, Colpaert FC (1979) Dependence creating properties of lipotropin C-fragment (β-endorphin): evidence for its internal control of behavior. Life Sci 24:195–202

    Google Scholar 

  • von Voigtlander PE, Lahti RA, Ludens JH (1983) U50, 488: A selective and structurally novel non-mu (kappa) opioid agonist. J Pharmacol Exp Ther 224:7–12

    Google Scholar 

  • Watson SJ, Akil H, Richard CW, Barchas JD (1978) Evidence for two separate opiate peptide neuronal systems. Nature 275:226–228

    Google Scholar 

  • Weber E, Evans CJ, Barchas JD (1982) Predominance of the amino-terminal octapeptide fragment of dynorphin in rat brain regions. Nature 299:77–79

    Google Scholar 

  • Wüster M, Schulz R, Herz A (1980) Opioid agonists and antagonists. Action on multiple opiate receptors. In: Way LL (ed) Endogenous and exogenous opioid agonists and antagonists. Pergamon Press, New York, pp 75–78

    Google Scholar 

  • Wüster M, Schulz R, Herz A (1981) Multiple opiate receptor in peripheral tissue preparations. Biochem Pharmacol 30: 1883–1887

    Google Scholar 

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Mucha, R.F., Millan, M.J. & Herz, A. Aversive properties of naloxone in non-dependent (naive) rats may involve blockade of central β-endorphin. Psychopharmacology 86, 281–285 (1985). https://doi.org/10.1007/BF00432214

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