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Effects of prenatal morphine on hypothalamic metabolism of neurotransmitters and gonadal and adrenal activities, during the early postnatal period in the rat

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Abstract

It is noteworthy that exposure to opiates during fetal development results in permanent changes in adults related to morphological, behavioral and biochemical measures; however little is known concerning the effects of such drugs in early postnatal life. We investigated in newborn rats the effects of prenatal morphine-exposure on both—the hypothalamic metabolism of norepinephrine (NE), serotonin (5 HT) and neuropeptide Y (NPY)—the activity of the hypothalamo-pituitary gonadal and adrenal axes. In a previous study performed in newborns of untreated mothers, we reported some sex-dependent changes in the metabolism of NE, 5 HT and NPY in the hypothalamus and an early activation of the gonadostimulating function and of the corticostimulating one. In control newborns from saline-treated mothers, a slight increase in the hypothalamic metabolism of NE (males) and 5 HT (males and females) was observed and it was comparable in both sexes. On the other hand, the hypothalamic content of NPY was unaffected in early postnatal period in newborn males as well as in females. These changes observed on hypothalamic metabolisms are temporally correlated with the early postnatal activation of the corticostimulating function in neonates of both sexes and that of the gonadostimulating one, mainly in males. Prenatal morphine exposure altered the hypothalamic metabolism of 5 HT which was increased mainly in newborn females but did not affect either the metabolism of NE or the NPY content of the hypothalamus. The more drastic effect of the prenatal morphine treatment is the atrophy and hypoactivity of the adrenals in newborns of both sexes at birth time and during the early postnatal period. In contrast morphine did not impair postnatal surge of the plasma testosterone level in male pups as well as late and slight increase of plasma estradiol in female ones.

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References

  1. Chasnoff, I. J. 1985. Effects of maternal narcotic vs non narcotic addition on neonatal neurobehavior and infant development. Pages 84–95,in T. M. Pinkert (Ed.), Consequences of Maternal Drug Abuse, National Institute on Drug Abuse, Washington, DC.

    Google Scholar 

  2. Vathy I., and Katay L. 1992. Effects of prenatal morphine on adult sexual behavior and brain catecholamines in rats. Develop. Brain Res. 68:125–131.

    Article  CAS  Google Scholar 

  3. Dupouy, J. P., and Chatelain, A. 1981. La fonction corticotrope dans la période périnatale: ontogenèse et régulation. J. Physiol. (Paris) 77:955–968.

    CAS  Google Scholar 

  4. Cohen, A., Chatelain, A., and Dupouy, J. P. 1983. Late pregnancy maternal and fetal time-course of plasma ACTH and corticosterone after continuous ether inhalation by pregnant rats. Cytoimmunological study of fetal hypophyseal cells. Biol. Neonate 43:220–228.

    PubMed  CAS  Google Scholar 

  5. Cohen, A., and Péchinot, D. 1979. Corticostérone dans le plasma de rat: taux maternel et fœtal en fin de gestation et pendant la parturition; fraction libre et liée. J. Physiol. 75:4A.

    Google Scholar 

  6. Kraiem, Z., Sack, J., and Brish, M. 1985. Serum cortisol levels: the first 10 days in full-term and preterm infants. Isr. J. Med. Sci. 21:170–172.

    PubMed  CAS  Google Scholar 

  7. Lee, M. M., Rajagopalam, L., Berg, G. J., and Moshang, J.r.T. 1989. Serum adrenal steroid concentrations in premature infants. J. Clin. Endocrinol. Metab. 69:1133–1136.

    Article  PubMed  CAS  Google Scholar 

  8. Buckingham, J. C., and Cooper, T. A. 1984. Differences in hypothalamo-pituitary-adrenocortical activity in the rat after acute and prolonged treatment with morphine. Neuroendocrinol. 38:411–417.

    CAS  Google Scholar 

  9. Einseinberg, R. M. 1994. Trimu-5, a μ2-opioid receptor agonist, stimulates the hypothalamo-pituitary-adrenal axis. Pharmacol. Biochem. Behav. 47:943–946.

    Article  Google Scholar 

  10. Martinez, J. A., Vargas, M. L., Fuente, T., Del Rio-Garcia, J., and Milanes, M. V. 1990. Plasma β-endorphin and cortisol levels in morphine-tolerant rats and in naloxone-induced withdrawal. Eur. J. Pharmacol. 182:117.

    Article  CAS  Google Scholar 

  11. Martinez-Pinero, M., Victoria Milanés, M., Alcaraz, C., and Vargas, M. L. 1994. Catecholaminergic mediation of morphine-induced activation of pituitary-adrenocortical axis in the rat: implication of α- and β-adrenoceptors. Brain Res. 668:122–128.

    Article  PubMed  CAS  Google Scholar 

  12. Vathy, I. 1993. Sexually dimorphic effects of prenatal morphine and cocaine on adult sexual behavior and brain catecholamines in rats. Hormones and Behavior 27:1–4.

    Article  PubMed  CAS  Google Scholar 

  13. Vathy, I., Rimanoczy, A., Eaton, R. C., and Katay, L. 1995. Sex dimorphic alterations in postnatal brain catecholamines after gestational morphine. Brain Res. Bull. 36:185–193.

    Article  PubMed  CAS  Google Scholar 

  14. Fuller, R. W. 1992. The involvement of serotonin in regulation of pituitary-adrenocortical function. Front. Neuroendocrinol. 13:250–270.

    PubMed  CAS  Google Scholar 

  15. Boudouresque, F. 1987. Régulation de la fonction corticosurrénaliénne chez le rat au cours du développement. Thèse de Doctorat d’Etat, Montpellier, France.

  16. Suda, T., Tozawa, F., Iwai, I., Sato, Y., Sumitomo, T., Nakano, Y., Yamada, M., and Demura, H. 1993. Neuropeptide Y increases the corticotropin-releasing factor messenger ribonucleic acid level in the rat hypothalamus. Molec. Brain Res. 18:311–315.

    Article  PubMed  CAS  Google Scholar 

  17. Vathy, I., Etgen, A. M., and Barfield, R. J. 1985. Effects of prenatal exposure to morphine on the development of sexual behavior in rats. Pharmacol. Biochem. Behav. 22:227–232.

    Article  PubMed  CAS  Google Scholar 

  18. Siddiqui, A., Soofia, H., Saeeda, S., and Syed, G. H. V. 1995. Morphine induces reproductive changes in female rats and their male offspring. Repord. Toxicol. 9:143–151.

    Article  CAS  Google Scholar 

  19. Corbier, P., Roffi, J., and Rhoda, J. 1983. Female sexual behavior in male rats: effect of hour of castration at birth. Physiol. and Behav. 30:613–616.

    Article  CAS  Google Scholar 

  20. Roffi, J., Chami, F., Corbier, P., and Edwards, S. A. 1987. Testicular hormones during the first few hours after birth augment the tendency of adult males to mount receptive females. Hormones and Behav. 39:523–527.

    Google Scholar 

  21. Lalau, J. D., Aubert, M. L., Carmignac, D. F., Grégoire, I., and Dupouy, J. P. 1990. Reduction in testicular function in rats. I. Reduction by specific gonadotropin-releasing hormone antagonist in fetal rats. Neuroendocrinology 51:284–288.

    PubMed  CAS  Google Scholar 

  22. Lalau, J. D., Aubert, M. L., Carmignac, D. F., Grégoire, I., and Dupouy, J. P. 1990. Reduction in testicular function in rats. II. Reduction by dexamethasone in fetal and neonatal rats. Neuroendocrinology 51:289–293.

    PubMed  CAS  Google Scholar 

  23. Corbier, P., Edwards, D. A., and Roffi, J. 1992. The neonatal testosterone surge: a comparative study. Arch. Int. Physiol. Bioch. Biophys. 100:127–131.

    CAS  Google Scholar 

  24. Siddiqui, A., and Gilmore, P. 1988. Regional differences in the catecholamine content of the rat brain: Effects of neonatal castration and androgenization. Acta Endocrinol. 118:483–494.

    PubMed  CAS  Google Scholar 

  25. Barraclough, C. A. 1992. Neural control of the synthesis and release of luteinizing hormone-releasing hormone. Functional anatomy of the neuroendocrine hypothalamus, vol. 168, Wiley, Chichester, Ciba Foundation Symposium, pp. 233–251.

    Google Scholar 

  26. Mendelson, S. D. 1992. A review and reevaluation of the role of serotonin in the modulation of lordosis behavior in the female rat. Neurosci. Biobehav. Rev. 16:309–350.

    Article  PubMed  CAS  Google Scholar 

  27. Slotkin, T. A., Whitmore, W. L., Salvaggio, M., and Seidler, F. J. 1979. Perinatal methadone addiction affects brain synaptic development of biogenic amine systems in the rat. Life Sci. 24:1223–1230.

    Article  PubMed  CAS  Google Scholar 

  28. Freeman, M. E. 1993. Neuropeptide Y: A unique member of the constellation of gonadotropin-releasing hormones. Endocrinology 133:2411–2412.

    Article  PubMed  CAS  Google Scholar 

  29. Sahu, A., Crowley, W. R., Kalra, P. S., and Kalra, S. P. 1992. A selective sexually dimorphic response in the median eminence neuropeptide Y. Brain Res. 573:235–242.

    Article  PubMed  CAS  Google Scholar 

  30. Urban, J. H., Bauer-Dantoin, A. C., and Levine, J. E. 1993. Neuropeptide Y gene expression in the arcuate nucleus: sexual dimorphism and modulation by testosterone. Endocrinology 132:139–145.

    Article  PubMed  CAS  Google Scholar 

  31. Pages, N., Orosco, M., Fournier, G., Rouch, C., Hafi, A., Gourch, A., Comoy, E., and Bohuon, C. 1991. The effects of chronic administration of morphine on the levels of brain and adrenal catecholamines and neuropeptide Y in rats. Gen. Pharmac. 22:943–947.

    CAS  Google Scholar 

  32. Lesage, J., Bernet, F., Montel, V., and Dupouy, J. P. 1996. Hypothalamic metabolism of neurotransmitters (serotonin, norepinephrine, dopamine) and NPY, and gonadal and adrenal activities, during the early postnatal period in the rat. Neurochem. Res. 21:87–96.

    PubMed  CAS  Google Scholar 

  33. Bernet, F., Maubert, E., Bernard, J., Montel, V., and Dupouy, J. P. 1994. In vitro steroidogenic effects of neuropeptide Y (NPY136), Y1 and Y2 receptor agonists (Leu31-Pro34 NPY, NPY18–36) and peptide YY (PYY) on rat adrenal capsule/zona glomerulosa. Regul, Peptides 52:187–193.

    Article  CAS  Google Scholar 

  34. Maubert, E., Dupouy, J. P., and Bernet, F. 1993. Effect of adrenal demedullation on neuropeptide Y content of the capsule/glomerulosa zone of the rat adrenal gland. Neurosci. Lett. 156:5–8.

    Article  PubMed  CAS  Google Scholar 

  35. Leret, M. L., Gonzalez, M., and Arahuetes, R. M. 1993. Effect of maternal deprivation on the content of catecholamines in fetal brain. Life Sci. 52:1609–1615.

    Article  PubMed  CAS  Google Scholar 

  36. Slotkin, T. A., Lappi, S. E., McCook, E. C., Tayyeb, M. I., Eylers, J. P., and Seidler, F. J. 1992. Glucocorticoids and the development of neuronal function: effects of prenatal dexamethasone exposure on central noradrenergic activity. Biol. Neonate 61:326–336.

    PubMed  CAS  Google Scholar 

  37. Vathy, I., Rimanoczy, A., Eaton, R. C., and Katay, L. 1994. Modulation of catecholamine turnover rate in brain regions of rats exposed prenatally to morphine. Brain Res. 662:209–215.

    Article  PubMed  CAS  Google Scholar 

  38. Kuhn, C. M., Windh, R. T., and Little, P. J. 1992. Effects of perinatal opiate addiction on neurochemical development of the brain. Development of the Central Nervous System: Effects of alcohol and opiates, pp. 341–361, Wiley-Liss, Inc.

  39. Grauer, S. M., Tao, R., and Auerbach, S. B. 1992. Morphine induces an increase in extracellular serotonin in the rat diencephalon. Brain Res. 599:277–282.

    Article  PubMed  CAS  Google Scholar 

  40. Hökfelt, T., Millhorn, D., Seroogy, K., Tsuruo, Y., Ceccatelli, S., Lindth, B., Meister, B., Melander, T., Schalling, M., Bartfai, T., and Terenius, L. 1987. Coexistence of peptides with classical neurotransmitters. Experientia 43:758–780.

    Google Scholar 

  41. Dupouy, J. P., Chatelain, A., Boudouresque, F., Conte-Devolx, B., and Oliver, C. 1987. Effects of chronic maternal Dexamethasone treatment on the hormones of the hypothalamo-pituitary-adrenal axis in the rat fetus. Biol. Neonate 52:216–222.

    Article  PubMed  CAS  Google Scholar 

  42. Whitnall, M. H. 1993. Regulation of the hypothalamic corticotropin-releasing hormone neurosecretory system. Progress in Neurobiol. 40:573–629.

    CAS  Google Scholar 

  43. Kuhn, C. M., Butler, S. R., and Schanberg, S. M. 1978. Selective depression of serum growth hormone during maternal deprivation in rat pups. Science 201:1034–1036.

    Article  PubMed  CAS  Google Scholar 

  44. Kacsoh, B., Meyers, J. S., Growley, W. R., and Grosvenor, C. E. 1990. Maternal modulation of growth hormone secretion in the neonatal rat: involvement of mother-offspring interactions. J. Endocrinol. 124:233–240.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Centre de Biologie Cellulaire, Neuroendocrinologie Expérimentale Neuroendocrinologie du Développement, J.E. 234, Université de Lille 1, 59655, Villeneuve d’Ascq, France

    J. Lesage, F. Bernet, V. Montel & J. P. Dupouy

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  1. J. Lesage
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  2. F. Bernet
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  3. V. Montel
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  4. J. P. Dupouy
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Lesage, J., Bernet, F., Montel, V. et al. Effects of prenatal morphine on hypothalamic metabolism of neurotransmitters and gonadal and adrenal activities, during the early postnatal period in the rat. Neurochem Res 21, 723–732 (1996). https://doi.org/10.1007/BF02527731

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