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. 1997 Nov 15;505(Pt 1):145–152. doi: 10.1111/j.1469-7793.1997.145bc.x

Local opioid inhibition and morphine dependence of supraoptic nucleus oxytocin neurones in the rat in vivo.

M Ludwig 1, C H Brown 1, J A Russell 1, G Leng 1
PMCID: PMC1160100  PMID: 9409478

Abstract

1. Single neurones of the rat supraoptic nucleus were recorded during microdialysis of naloxone onto the ventral surface of the nucleus in anaesthetized rats. We used this combination of techniques to test whether the acute or chronic effects of systemically or centrally applied opioids upon oxytocin cell activity were due to actions of the opioids within the nucleus itself. 2. Supraoptic nucleus oxytocin neurones were identified antidromically and by an excitatory response to intravenously injected cholecystokinin. Acute intravenous injection of the kappa-agonist U50488H or the mu-agonist morphine (1-5 mg kg-1) reduced the firing rate of identified oxytocin neurones by 97.7 +/- 4.8% (n = 6) and 94.1 +/- 4.1% (n = 7), respectively. The inhibition by each of these opioids was completely reversed after administration by microdialysis (retrodialysis) of the opioid antagonist naloxone (0.1-1.0 microgram microliter-1 at 2 microliters min-1) onto the exposed ventral surface of the supraoptic nucleus. 3. Retrodialysis of naloxone (0.1-10.0 micrograms microliter-1) onto the supraoptic nucleus of rats made dependent by intracerebroventricular morphine infusion for 5 days increased the firing rate of oxytocin neurones from 0.9 +/- 0.4 to 3.1 +/- 0.7 spikes s-1 (P < 0.05, n = 6). This increase in firing rate from basal was 58.5 +/- 15.1% of that following subsequent intravenously injected naloxone (5 mg kg-1). 4. Thus, the acute inhibition of supraoptic nucleus oxytocin neurones which results from systemic administration of opioid agonists primarily occurs within the supraoptic nucleus itself, since the antagonist naloxone was effective when given into the supraoptic nucleus. Furthermore, oxytocin neurones develop morphine dependence by a mechanism which is distinct from an action on their distant afferent inputs. Nevertheless, withdrawal excitation of these afferent inputs may enhance the magnitude of oxytocin neurone withdrawal excitation.

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Selected References

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  1. Aghajanian G. K., Kogan J. H., Moghaddam B. Opiate withdrawal increases glutamate and aspartate efflux in the locus coeruleus: an in vivo microdialysis study. Brain Res. 1994 Feb 4;636(1):126–130. doi: 10.1016/0006-8993(94)90186-4. [DOI] [PubMed] [Google Scholar]
  2. Aghajanian G. K. Tolerance of locus coeruleus neurones to morphine and suppression of withdrawal response by clonidine. Nature. 1978 Nov 9;276(5684):186–188. doi: 10.1038/276186a0. [DOI] [PubMed] [Google Scholar]
  3. Armstrong W. E., Schöler J., McNeill T. H. Immunocytochemical, Golgi and electron microscopic characterization of putative dendrites in the ventral glial lamina of the rat supraoptic nucleus. Neuroscience. 1982 Mar;7(3):679–694. doi: 10.1016/0306-4522(82)90074-4. [DOI] [PubMed] [Google Scholar]
  4. Benveniste H., Hüttemeier P. C. Microdialysis--theory and application. Prog Neurobiol. 1990;35(3):195–215. doi: 10.1016/0301-0082(90)90027-e. [DOI] [PubMed] [Google Scholar]
  5. Brown C. H., Munro G., Murphy N. P., Leng G., Russell J. A. Activation of oxytocin neurones by systemic cholecystokinin is unchanged by morphine dependence or withdrawal excitation in the rat. J Physiol. 1996 Nov 1;496(Pt 3):787–794. doi: 10.1113/jphysiol.1996.sp021727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cunningham E. T., Jr, Sawchenko P. E. Reflex control of magnocellular vasopressin and oxytocin secretion. Trends Neurosci. 1991 Sep;14(9):406–411. doi: 10.1016/0166-2236(91)90032-p. [DOI] [PubMed] [Google Scholar]
  7. Done C., Silverstone P., Sharp T. Effect of naloxone-precipitated morphine withdrawal on noradrenaline release in rat hippocampus in vivo. Eur J Pharmacol. 1992 May 14;215(2-3):333–336. doi: 10.1016/0014-2999(92)90052-6. [DOI] [PubMed] [Google Scholar]
  8. Gold M. S., Redmond D. E., Jr, Kleber H. D. Clonidine blocks acute opiate-withdrawal symptoms. Lancet. 1978 Sep 16;2(8090):599–602. doi: 10.1016/s0140-6736(78)92823-4. [DOI] [PubMed] [Google Scholar]
  9. Gross P. M., Sposito N. M., Pettersen S. E., Fenstermacher J. D. Differences in function and structure of the capillary endothelium in the supraoptic nucleus and pituitary neural lobe of rats. Evidence for the supraoptic nucleus as an osmometer. Neuroendocrinology. 1986;44(4):401–407. doi: 10.1159/000124678. [DOI] [PubMed] [Google Scholar]
  10. Inenaga K., Nagatomo T., Nakao K., Yanaihara N., Yamashita H. Kappa-selective agonists decrease postsynaptic potentials and calcium components of action potentials in the supraoptic nucleus of rat hypothalamus in vitro. Neuroscience. 1994 Jan;58(2):331–340. doi: 10.1016/0306-4522(94)90039-6. [DOI] [PubMed] [Google Scholar]
  11. Jhamandas J. H., Harris K. H., Petrov T., Jhamandas K. H. Activation of nitric oxide-synthesizing neurones during precipitated morphine withdrawal. Neuroreport. 1996 Nov 25;7(18):2843–2846. doi: 10.1097/00001756-199611250-00006. [DOI] [PubMed] [Google Scholar]
  12. Leng G., Russell J. A., Grossmann R. Sensitivity of magnocellular oxytocin neurones to opioid antagonists in rats treated chronically with intracerebroventricular (i.c.v.) morphine. Brain Res. 1989 Apr 10;484(1-2):290–296. doi: 10.1016/0006-8993(89)90372-7. [DOI] [PubMed] [Google Scholar]
  13. Mansour A., Fox C. A., Burke S., Akil H., Watson S. J. Immunohistochemical localization of the cloned mu opioid receptor in the rat CNS. J Chem Neuroanat. 1995 May;8(4):283–305. doi: 10.1016/0891-0618(95)00055-c. [DOI] [PubMed] [Google Scholar]
  14. Mansour A., Khachaturian H., Lewis M. E., Akil H., Watson S. J. Anatomy of CNS opioid receptors. Trends Neurosci. 1988 Jul;11(7):308–314. doi: 10.1016/0166-2236(88)90093-8. [DOI] [PubMed] [Google Scholar]
  15. Murphy N. P., Onaka T., Brown C. H., Leng G. The role of afferent inputs to supraoptic nucleus oxytocin neurons during naloxone-precipitated morphine withdrawal in the rat. Neuroscience. 1997 Sep;80(2):567–577. doi: 10.1016/s0306-4522(97)00142-5. [DOI] [PubMed] [Google Scholar]
  16. Nestler E. J., Alreja M., Aghajanian G. K. Molecular and cellular mechanisms of opiate action: studies in the rat locus coeruleus. Brain Res Bull. 1994;35(5-6):521–528. doi: 10.1016/0361-9230(94)90166-x. [DOI] [PubMed] [Google Scholar]
  17. Nye H. E., Nestler E. J. Induction of chronic Fos-related antigens in rat brain by chronic morphine administration. Mol Pharmacol. 1996 Apr;49(4):636–645. [PubMed] [Google Scholar]
  18. Onaka T., Luckman S. M., Guevara-Guzman R., Ueta Y., Kendrick K., Leng G. Presynaptic actions of morphine: blockade of cholecystokinin-induced noradrenaline release in the rat supraoptic nucleus. J Physiol. 1995 Jan 1;482(Pt 1):69–79. doi: 10.1113/jphysiol.1995.sp020500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pittman Q. J., Hatton J. D., Bloom F. E. Morphine and opioid peptides reduce paraventricular neuronal activity: studies on the rat hypothalamic slice preparation. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5527–5531. doi: 10.1073/pnas.77.9.5527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pumford K. M., Russell J. A., Leng G. Effects of the selective kappa-opioid agonist U50,488 upon the electrical activity of supraoptic neurones in morphine-tolerant and morphine-naive rats. Exp Brain Res. 1993;94(2):237–246. doi: 10.1007/BF00230291. [DOI] [PubMed] [Google Scholar]
  21. Raby W. N., Renaud L. P. Dorsomedial medulla stimulation activates rat supraoptic oxytocin and vasopressin neurones through different pathways. J Physiol. 1989 Oct;417:279–294. doi: 10.1113/jphysiol.1989.sp017801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rayner V. C., Robinson I. C., Russell J. A. Chronic intracerebroventricular morphine and lactation in rats: dependence and tolerance in relation to oxytocin neurones. J Physiol. 1988 Feb;396:319–347. doi: 10.1113/jphysiol.1988.sp016964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Russell J. A., Pumford K. M., Bicknell R. J. Contribution of the region anterior and ventral to the third ventricle to opiate withdrawal excitation of oxytocin secretion. Neuroendocrinology. 1992 Feb;55(2):183–192. doi: 10.1159/000126113. [DOI] [PubMed] [Google Scholar]
  24. Sharif N. A., Hughes J. Discrete mapping of brain Mu and delta opioid receptors using selective peptides: quantitative autoradiography, species differences and comparison with kappa receptors. Peptides. 1989 May-Jun;10(3):499–522. doi: 10.1016/0196-9781(89)90135-6. [DOI] [PubMed] [Google Scholar]
  25. Silverstone P. H., Done C., Sharp T. Clonidine but not nifedipine prevents the release of noradrenaline during naloxone-precipitated opiate withdrawal: an in vivo microdialysis study in the rat. Psychopharmacology (Berl) 1992;109(1-2):235–238. doi: 10.1007/BF02245506. [DOI] [PubMed] [Google Scholar]
  26. Stornetta R. L., Norton F. E., Guyenet P. G. Autonomic areas of rat brain exhibit increased Fos-like immunoreactivity during opiate withdrawal in rats. Brain Res. 1993 Oct 8;624(1-2):19–28. doi: 10.1016/0006-8993(93)90055-r. [DOI] [PubMed] [Google Scholar]
  27. Sumner B. E., Coombes J. E., Pumford K. M., Russell J. A. Opioid receptor subtypes in the supraoptic nucleus and posterior pituitary gland of morphine-tolerant rats. Neuroscience. 1990;37(3):635–645. doi: 10.1016/0306-4522(90)90095-l. [DOI] [PubMed] [Google Scholar]
  28. Taylor J. R., Elsworth J. D., Garcia E. J., Grant S. J., Roth R. H., Redmond D. E., Jr Clonidine infusions into the locus coeruleus attenuate behavioral and neurochemical changes associated with naloxone-precipitated withdrawal. Psychopharmacology (Berl) 1988;96(1):121–134. doi: 10.1007/BF02431544. [DOI] [PubMed] [Google Scholar]
  29. Wakerley J. B., Noble R., Clarke G. Effects of morphine and D-Ala, D-Leu enkephalin on the electrical activity of supraoptic neurosecretory cells in vitro. Neuroscience. 1983 Sep;10(1):73–81. doi: 10.1016/0306-4522(83)90081-7. [DOI] [PubMed] [Google Scholar]
  30. Yang C. R., Senatorov V. V., Renaud L. P. Organum vasculosum lamina terminalis-evoked postsynaptic responses in rat supraoptic neurones in vitro. J Physiol. 1994 May 15;477(Pt 1):59–74. doi: 10.1113/jphysiol.1994.sp020171. [DOI] [PMC free article] [PubMed] [Google Scholar]

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