Neuromodulatory Action of Opioid Peptides on Hypothalamic Neurons

  • Jean-Pierre Wuarin
  • F. Edward Dudek
Part of the Drug and Alcohol Abuse Reviews book series (DAAR, volume 6)


The control of the endocrine system is one of the most important functions of the hypothalamus. Opium and its derivatives have long been known to alter release of pituitary hormones. Heroin remains one of the most widely abused illegal drugs, and the understanding of the actions of its active metabolite, morphine, on the endocrine system is still fragmentary. With the parallel discovery of the endogenous opioids and of opioid receptor sites and pathways in the brain, and in particular in the hypothalamus, the hypothesis emerged that these peptides play an important role in the control of neurohypophysial secretion by influencing directly the activity of the neuroendocrine cells. This chapter focuses on electrophysiological studies aimed at defining the influence of opioids on three of the most important nuclei of the neuroendocrine hypothalamus: the supraoptic, paraventricular, and arcuate nuclei.


Opioid Peptide Paraventricular Nucleus Arcuate Nucleus Supraoptic Nucleus Inhibitory Synaptic Input 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    G. I. Hatton (1990) Emerging concepts of structure-function dynamics in adult brain: the hypothalamo-neurohypophysial system.Prog. Neurobiol. 34, 437–504.PubMedCrossRefGoogle Scholar
  2. 2.
    L. P. Renaud and C. W. Bourque (1991) Neurophysiology and neuropharmacology of hypothalamic magnocellular neurons secreting vasopressin and oxytocin.Prog. Neurobiol. 36, 131–169.PubMedCrossRefGoogle Scholar
  3. 3.
    R. J. Bicknell (1993) Opioids in the neurohypophysial system, inHandbook of Experimental Pharmacologyvol. 104, II. A. Hertz, ed. Springer-Verlag, Heidelberg, pp. 525–550.Google Scholar
  4. 4.
    R. J. Bicknell, G. Leng, J. A. Russel, R. G. Dyer, S. Mansfield, and B. G. Zhao (1988) Hypothalamic opioid mechanisms controlling oxytocin neurones during parturition.Brain Res. Bull. 20, 743–749.PubMedCrossRefGoogle Scholar
  5. 5.
    A. J. Douglas, S. Dye, G. Leng, J. A. Russel, and R. J. Bicknell (1993) Endogenous opioid regulation of oxytocin secretion through pregnancy in the rat.J. Neuroendocrinol. 5, 307–314.PubMedCrossRefGoogle Scholar
  6. 6.
    B.-G. Zhao, C. Chapman, and R. J. Bicknell (1988) Functional x-opioid receptors on oxytocin and vasopressin nerve terminals isolated from the rat neurohypophysis.Brain Res. 462, 62–66.PubMedCrossRefGoogle Scholar
  7. 7.
    C. W. Bourque (1990) Intraterminal recordings from the rat neurohypophysis in vitro.J. Physiol. 421, 247–262.PubMedGoogle Scholar
  8. 8.
    C. W. Bourque (1991) Activity-dependent modulation of nerve terminal excitation in a mammalian peptidergic system.Trends Neurosci. 14, 28–30.PubMedCrossRefGoogle Scholar
  9. 9.
    M. B. Jackson, A. Konnerth, and G. J. Augustine (1991) Action potential broadening and frequency-dependent facilitation of calcium signals in pituitary nerve terminals.Proc. Natl. Acad. Sci. USA 88, 380–384.PubMedCrossRefGoogle Scholar
  10. 10.
    M. I. Banks, K. Bielefeldt, and M. B. Jackson (1993) Opioid modulation of K and Ca currents in mammalian nerve terminals.Soc. Neurosci. Abstr. 19, 1523.Google Scholar
  11. 11.
    L. P. Renaud, C. W. Bourque, T. A. Day, A. V. Ferguson, and J. C. R. Randle (1985) Electrophysiology of mammalian hypothalamic supraoptic and paraventricular neurosecretory cells, inThe Electrophysiology of the Secretory Cell. A. M. Poisner and J. Trifaro, eds. Elsevier Science, BV, Amsterdam, pp. 166–194.Google Scholar
  12. 12.
    R. D. Andrew and F. E. Dudek (1983) Burst discharge in mammalian neuroendocrine cells involves an intrinsic regenerative mechanism.Science 221, 1050–1052.PubMedCrossRefGoogle Scholar
  13. 13.
    C. W. Bourque and L. P. Renaud (1990) Electrophysiology of mammalian magno-cellular vasopressin and oxytocin neurosecretory neurons.Frontiers in Neuroendocrinol.3, 183–212.Google Scholar
  14. 14.
    B. Hu and C. W. Bourque (1992) NMDA receptor-mediated rhythmic bursting activity in rat supraoptic nucleus neurones in vitroJ. Physiol. 458, 667–687.PubMedGoogle Scholar
  15. 15.
    L. P. Renaud (1987) Magnocellular neuroendocrine neurons: update on intrinsic properties, synaptic inputs and neuropharmacology.Trends Neurosci. 10, 498–502.CrossRefGoogle Scholar
  16. 16.
    R. J. Bicknell (1988) Optimizing release from peptide hormone secretory nerve terminals.J. Exp. Biol. 139, 51–65.PubMedGoogle Scholar
  17. 17.
    C. W. Bourque, S. H. Oliet, K. Kirkpatrick, D. Richard, and T. E. Fisher (1993) Extrinsic and intrinsic modulatory mechanisms involved in regulating the electrical activity of supraoptic neurons.Ann. NY Acad. Sci. 689, 512–519.PubMedCrossRefGoogle Scholar
  18. 18.
    M. Muehlethaler, B. H. Gaehwiler, and J. J. Dreifuss (1980) Enkephalin-induced inhibition of hypothalamic paraventricular neurons.Brain Res. 197, 264–268.PubMedCrossRefGoogle Scholar
  19. 19.
    Q. J. Pittman, J. D. Hatton, and F. E. Bloom (1980) Morphine and opioid peptides reduce paraventricular neuronal activity: study on the rat hypothalamic slice preparation.Proc. Natl. Acad. Sci. USA 77, 5525–5531.CrossRefGoogle Scholar
  20. 20.
    J. B. Wakerley, R. Noble, and G. Clarke (1983) Effects of morphine and o-ala,DLeu enkephalin on the electrical activity of supraoptic neurosecretory cells in vitro.Neuroscience 10, 73–81.PubMedCrossRefGoogle Scholar
  21. 21.
    R. J. Bicknell, G. Leng, D. W. Lincoln, and J. A. Russel (1988) Naloxone excites oxytocin neurones in the supraoptic nucleus of lactating rats after chronic morphine treatment.J. Physiol. 396, 297–317.PubMedGoogle Scholar
  22. 22.
    K. Inenaga, H. Imura, N. Yanaihara, and H. Yamashita (1990) Kappa-selective opioid receptors agonists leumorphin and dynorphin inhibit supraoptic neurons in rat hypothalamic slice preparations.J. Neuroendocrinol. 2, 389–395.PubMedCrossRefGoogle Scholar
  23. 23.
    J.-P. Wuarin, M. Dubois-Dauphin, M. Raggenbass, and J. J. Dreifuss (1988) Effect of opioid peptides on the paraventricular nucleus of the guinea pig hypothalamus is mediated by.t-type receptors.Brain Res. 445, 289–296.PubMedCrossRefGoogle Scholar
  24. 24.
    N. W. Hoffman, J. G. Tasker, and F. E. Dudek (1991) Immunohistochemical differentiation of electrophysiologically defined neuronal populations in the region of the rat hypothalamic paraventricular nucleus.J. Comp. Neurol. 307, 405–416.PubMedCrossRefGoogle Scholar
  25. 25.
    J. G. Tasker and F. E. Dudek (1991) Electrophysiological properties of neurones in the region of the paraventricular nucleus of rat hypothalamus.J. Physiol. 434, 271–293.PubMedGoogle Scholar
  26. 26.
    J. G. Tasker and F. E. Dudek (1993) Local inhibitory synaptic inputs to neurones of the paraventricular nucleus in slices of rat hypothalamus.J. Physiol. 469, 179–192.PubMedGoogle Scholar
  27. 27.
    J.-P. Wuarin and F. E. Dudek (1990) Direct effects of and opioid peptide selective for µ-receptors: intracellular recordings in the paraventricular and supraoptic nuclei of the guinea-pig.Neuroscience 36, 291–298.PubMedCrossRefGoogle Scholar
  28. 28.
    M. Kasai, J. G. Tasker, J.-P. Wuarin, and F. E. Dudek (1993) Membrane properties of identified guinea-pig paraventricular neurons and their response to an opioid 4-receptor agonist: evidence for an increase in K` conductance.J. Neuroendocrinol. 5, 233–240.PubMedCrossRefGoogle Scholar
  29. 29.
    M. Kasai, J.-P. Wuarin, and F. E. Dudek (1990) Responses of paraventricular nucleus neurons to an opioid selective for g-receptors in guinea pig.Soc. Neurosci. Abstr. 16, 574.Google Scholar
  30. 30.
    J. T. Williams, R.A. North, and T. Tokimasa (1988) Inward rectification of resting and opiate-activated potassium currents in rat locus coeruleus neurons.J. Neurosci. 8, 4299–4306.PubMedGoogle Scholar
  31. 31.
    M. Miyake, M. J. Christie, and R. A. North (1989) Single potassium channels opened by opioids in rat locus ceruleus neurons.Proc. Natl. Acad. Sci. USA 86, 3419–3422.PubMedCrossRefGoogle Scholar
  32. 32.
    T. Hökfelt, B. Meister, M. J. Villar, S. Ceccatelli, R. Cortés, M. Schalling, and B. Everitt (1989) Hypothalamic neurosecretory systems and their messenger moleculesActa Physiol. Scand. 136(Suppl. 583), 105–111.Google Scholar
  33. 33.
    M. D. Loose and M. J. Kelly (1990) Opioids act at µ-receptors to hyperpolarize arcuate neurons via an inwardly rectifying potassium conductance.Brain Res. 513, 15–23.PubMedCrossRefGoogle Scholar
  34. 34.
    M. J. Kelly, M. D. Loose, and O. K. Ronnekleiv (1990) Opioids hyperpolarize 3-endorphins neurons via µ-receptor activation of a potassium conductance.Neuroendocrinology 52, 268–275.PubMedCrossRefGoogle Scholar
  35. 35.
    M. D. Loose, O. K. Ronnekleiv, and M. J. Kelly (1990) Membrane properties and response to opioids of identified dopamine neurons in the guinea pig hypothalamus.J. Neurosci. 10, 3625–3634.Google Scholar
  36. 36.
    M. D. Loose, O. K. Ronnekleiv, and M. J. Kelly (1991) Neurons in the rat arcuate nucleus are hyperpolarized by GABABand µ-opioid receptor agonists: evidence for convergence at a ligand-gated potassium conductance.Neuroendocrinology 54, 537–544.PubMedCrossRefGoogle Scholar
  37. 37.
    M. J. Kelly, M. D. Loose, and O. K. Ronnekleiv (1992) Estrogen suppresses gopioid-and GABAB-mediated hyperpolarization of hypothalamic arcuate neurons.J. Neurosci. 12, 2745–2750.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Jean-Pierre Wuarin
  • F. Edward Dudek

There are no affiliations available

Personalised recommendations