Journal of Molecular Neuroscience

, Volume 4, Issue 1, pp 21–28 | Cite as

Chronic treatment of newborn rats with naltrexone alters astrocyte production of nerve growth factor

  • Kunihiko Mitsuo
  • Joan P. Schwartz


Newborn rats were treated with the opiate antagonist naltrexone daily for 1–2 wk in order to examine the effects of endogenous opioid peptides on astrocytes during CNS development. Nerve growth factor (NGF) and cyclic AMP were measured in astrocytes cultured from cerebellum, striatum, and hippocampus of 1 d, 1 wk, and 2 wk postnatal rats. Cerebellar and striatal, but not hippocampal, astrocytes prepared from naltrexone-treated animals produced higher levels of NGF than those from controls. The turnover rate of cyclic AMP, measured following treatment of the cells with forskolin in the presence of the phosphodiesterase inhibitor IBMX, was increased in naltrexone-derived cerebellar and striatal astrocytes. Opiate receptors could not be detected on the cultured astrocytes, either by direct binding of3H-etorphine or by modulation of cyclic AMP content. These results suggest that endogenous opioid peptides may function indirectly to alter trophic factor synthesis in astrocytes.

Index Entries

Opioid peptides cyclic AMP opiate receptors CNS development 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Brenneman D. E., Nicol T., Warren D., and Bowers L. M. (1990) Vasoactive intestinal peptide: a neuro-trophic releasing agent and an astroglial mitogen.J. Neurosci. Res. 25, 386–394.PubMedCrossRefGoogle Scholar
  2. Carman-Krzan M., Vige X., and Wise B. C. (1991) Regulation by interleukin-1 of nerve growth factor secretion and nerve growth factor mRNA expression in rat primary astroglial cultures.J. Neurochem. 56, 636–643.PubMedCrossRefGoogle Scholar
  3. Cholewinski A. J. and Wilkin G. P. (1988) Astrocytes from forebrain, cerebellum, and spinal cord differ in their responses to vasoactive intestinal peptide.J. Neurochem. 51, 1626–1633.PubMedCrossRefGoogle Scholar
  4. Delitala G., Motta M., and Serio M., eds. (1984)The Opioid Modulation of Endocrine Function, Raven, New York.Google Scholar
  5. Eriksson P. S., Hansson E., and Rönnbäck L. (1990) δ and K opiate receptors in primary astroglial cultures from rat cerebral cortex.Neurochem. Res. 15, 1123–1126.PubMedCrossRefGoogle Scholar
  6. Gadient R. A., Cron K. C., and Otten U. (1990) Interleukin-1 beta and tumor necrosis factor-alpha synergistically stimulate nerve growth factor (NGF) release from cultured rat astrocytes.Neurosci. Lett. 117, 335–340.PubMedCrossRefGoogle Scholar
  7. Hendrickson C. M. and Lin S. (1980) Opiate receptors in highly purified neuronal cell populations isolated in bulk from embryonic chick brain.Neuropharmacology 19, 731–739.PubMedCrossRefGoogle Scholar
  8. Kimmelberg H. K. (1988)Glial Cell Receptors, Raven, New York.Google Scholar
  9. Large T. H., Bodary S. C., Clegg D. O., Weskamp G., Otten U., and Reichardt L. F. (1986) Nerve growth factor gene expression in the developing rat brain.Science 234, 352–355.PubMedCrossRefGoogle Scholar
  10. Lowry O. H., Rosebrough N. J., Farr A. L., and Randall R. J. (1951) Protein measurement with the Folin phenol reagent.J. Biol. Chem. 193, 265–275.PubMedGoogle Scholar
  11. Maderspach K. and Solomonia R. (1988) Glial and neuronal opioid receptors: apparent positive cooperativity observed in intact cultured cells.Brain Res. 441, 41–47.PubMedCrossRefGoogle Scholar
  12. McCarthy K. D. and DeVellis J. (1980) Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue.J. Cell Biol. 85, 890–902.PubMedCrossRefGoogle Scholar
  13. Mobley W. C., Woo J. E., Edwards R. H., Riopelle R. J., Longo F. M., Weskamp G., Otten U., Valletta J. S., and Johnston M. V. (1989) Developmental regulation of nerve growth factor and its receptor in the rat caudate-putamen.Neuron 3, 655–664.PubMedCrossRefGoogle Scholar
  14. Pearce B., Cambray-Deakin M., and Murphy S. (1985) Astrocyte opioid receptors: activation modifies the noradrenaline-evoked increase in 2-[14C]deoxyglucose incorporation into glycogen.Neurosci. Lett. 55, 157–160.PubMedCrossRefGoogle Scholar
  15. Rougon G., Noble M., and Mudge A. W. (1983) Neuro-peptides modulate the β-adrenergic response of purified astrocytes in vitro.Nature 305, 715–717.PubMedCrossRefGoogle Scholar
  16. Schwartz J. P. (1992) Neurotransmitters as neurotrophic factors: a new set of functions.Int. Rev. Neurobiol. 34, 1–23.PubMedCrossRefGoogle Scholar
  17. Schwartz J. P. and Mishler K. (1990) β-Adrenergic receptor regulation, through cyclic AMP, of nerve growth factor expression in rat cortical and cerebellar astrocytes.Cell. Mol. Neurobiol. 10, 447–457.PubMedCrossRefGoogle Scholar
  18. Schwartz J. P. and Passonneau J. V. (1974) Cyclic AMP-mediated induction of the cyclic AMP phosphodiesterase of C6 glioma cells.Proc. Natl. Acad. Sci. USA 71, 3844–3848.PubMedCrossRefGoogle Scholar
  19. Schwartz J. P. and Wilson D. J. (1992) Preparation and characterization of type 1 astrocytes cultured from adult rat cortex, cerebellum, and striatum.Glia 5, 75–80.PubMedCrossRefGoogle Scholar
  20. Slotkin T. A., Seidler F. J., and Whitmore W. L. (1980) Effects of maternal methadone administration on ornithine decarboxylase in brain and heart of the offspring: relationships of enzyme activity to dose and to growth impairment in the rat.Life Sci. 26, 861–867.PubMedCrossRefGoogle Scholar
  21. Smith A. A., Hui F. W., and Crofford M. J. (1977) Inhibition of growth in young mice treated with d,1-methadone.Eur. J. Pharmacol. 43, 307–314.PubMedCrossRefGoogle Scholar
  22. Stiene-Martin A. and Hauser K. F. (1990) Opioid-dependent growth of glial cultures: suppression of astrocyte DNA synthesis by met-enkephalin.Life Sci. 46, 91–98.PubMedCrossRefGoogle Scholar
  23. Vaysse P. J-J., Zukin R. S., Fields K. L., and Kessler J. A. (1990) Characterization of opioid receptors in cultured neurons.J. Neurochem. 55, 624–631.PubMedCrossRefGoogle Scholar
  24. Whitaker-Azmitia P. M., Murphy R., and Azmitia E. C. (1990) Stimulation of astroglial 5-HT1A receptors releases the serotonergic growth factor, protein S-100, and alters astroglial morphology.Brain Res. 528, 155–158.PubMedCrossRefGoogle Scholar
  25. Whittemore S. R., Ebendal T., Lärkfors L., Olson L., Seiger A., Strömberg I., and Persson H. (1986) Developmental and regional expression of β-nerve growth factor messenger RNA and protein in the rat central nervous system.Proc. Natl. Acad. Sci. USA 83, 817–821.PubMedCrossRefGoogle Scholar
  26. Wilson G. S., McCreary R., Kean J., and Baxter J. C. (1979) The development of preschool children of heroin-addicted mothers: a controlled study.Pediatrics 63, 135–141.PubMedGoogle Scholar
  27. Zagon I. S. and McLaughlin P. J. (1983) Increased brain size and cellular content in infant rats treated with an opiate antagonist.Science 221, 1179–1180.PubMedCrossRefGoogle Scholar
  28. Zagon I. S. and McLaughlin P. J. (1985) Naltrexone’s influence on neurobehavioral development.Pharmacol. Biochem. Behav. 22, 441–448.PubMedCrossRefGoogle Scholar
  29. Zagon I. S. and McLaughlin P. J. (1986a) Opioid antagonist-induced modulation of cerebral and hippocampal development: histological and morphometric studies.Dev. Brain Res. 28, 233–246.CrossRefGoogle Scholar
  30. Zagon I. S. and McLaughlin P. J. (1986b) Opioid antagonist (naltrexone) modulation of cerebellar development: histological and morphometric studies.J. Neurosci. 6, 1424–1432.PubMedGoogle Scholar

Copyright information

© Humana Press, Inc 1993

Authors and Affiliations

  • Kunihiko Mitsuo
    • 1
  • Joan P. Schwartz
    • 1
  1. 1.Clinical Neuroscience Branch, National Institute of Neurological Disorders and StrokeNational Institutes of HealthBethesda

Personalised recommendations