The Cerebellum

, Volume 2, Issue 3, pp 184–195

Selective vulnerability of cerebellar granule neuroblasts and their progeny to drugs with abuse liability

  • Kurt F. Hauser
  • Valeriya K. Khurdayan
  • Robin J. Goody
  • Avindra Nath
  • Alois Saria
  • James R. Pauly
Article

Abstract

Cerebellar development is shaped by the interplay of genetic and numerous environmental factors. Recent evidence suggests that cerebellar maturation is acutely sensitive to substances with abuse liability including alcohol, opioids, and nicotine. Assuming substance abuse disrupts cerebellar maturation, a central question is: what are the basic mechanisms underlying potential drug-induced developmental defects? Evidence reviewed herein suggests that the maturation of granule neurons and their progeny are intrinsically affected by several classes of substances with abuse liability. Although drug abuse is also likely to target directly other cerebellar neuron and glial types, such as Purkinje cells and Bergmann glia, findings in isolated granule neurons suggest that they are often the principle target for drug actions. Developmental events that are selectively disrupted by drug abuse in granule neurons and/or their neuroblast precursors include proliferation, migration, differentiation (including neurite elaboration and synapse formation), and programmed cell death. Moreover, different classes of drugs act through distinct molecular mechanisms thereby disrupting unique aspects of development. For example, drug-induced perturbations in: (i) neurotransmitter biogenesis; (ii) ligand and ion-gated receptor function and their coupling to intracellular effectors; (iii) neurotrophic factor biogenesis and signaling; and (iv) intercellular adhesion are all likely to have significant effects in shaping developmental outcome. In addition to identifying therapeutic strategies for drug abuse intervention, understanding the mechanisms by which drugs affect cellular maturation is likely to provide a better understanding of the neurochemical events that normally shape central nervous system development.

Keywords

neuroblast proliferation cerebellar development programmed cell death nicotinic acetylcholinergic receptors opioid receptors heroin nicotine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Manto M-U, Jacquy J. Other cerebellotoxic agents. In: Manto M-U, Pandolfo M, editors. The Cerebellum and its Disorders. 1st edn. Cambridge: Cambridge University Press, 2002: 342–366.Google Scholar
  2. 2.
    Ramoń Y, Cajal S. Studies on Vertebrate Neurogenesis. Springfield, Il.: Charles C. Thomas, 1960.Google Scholar
  3. 3.
    Rakic P. Neuron-glia relationship during granule cell migration in developing cerebellar cortex. A Golgi and electronmicroscopic study in Macacus rhesus. J Comp Neurol 1971; 141: 283–312.PubMedCrossRefGoogle Scholar
  4. 4.
    Airman J. Postnatal development of the cerebellar cortex in the rat. I. The external germinal layer and the transitional molecular layer. J Comp Neurol 1972; 145: 353–398.CrossRefGoogle Scholar
  5. 5.
    Herrup K, Kuemerle B. The compartmentalization of the cerebellum. Annu Rev Neurosci 1997; 20: 61–90.PubMedCrossRefGoogle Scholar
  6. 6.
    Hawkes R, Herrup K. Aldolase C/zebrin II and the regionalization of the cerebellum. J Mol Neurosci 1995; 6: 147–158.PubMedCrossRefGoogle Scholar
  7. 7.
    Goldowitz D, Hamre KM, Przyborski SA, Ackerman SL. Granule cells and cerebellar boundaries: analysis of Unc5h3 mutant chimeras. J Neurosci 2000; 20: 4129–4137.PubMedGoogle Scholar
  8. 8.
    Goldowitz D, Hamre K. The cells and molecules that make a cerebellum. Trends Neurosci 1998; 21: 375–382.PubMedCrossRefGoogle Scholar
  9. 9.
    Mullen RJ, Hamre KM, Goldowitz D. Cerebellar mutant mice and chimeras revisited. Perspect Dev Neurobiol 1997; 5: 43–55.PubMedGoogle Scholar
  10. 10.
    Larseil O. The morphogenesis and adult pattern of the lobules and fissures of the cerebellum of the white rat. J Comp Neurol 1952; 97: 281–356.CrossRefGoogle Scholar
  11. 11.
    Mugnaini E. Ultrastructural studies on the cerebellar histogenesis. II. Maturation of nerve poplations and establishment of synaptic connections in the cerebellar cortex of the chick. In: Llinás R, editor. Neurobiology of Cerebellar Evolution and Development. Chicago: Institute for Biomedical Research, American Medical Association, 1969: 749–801.Google Scholar
  12. 12.
    Miale IL, Sidman RL. An autoradiographic analysis of histogenesis in the mouse cerebellum. Exp Neurol 1961; 4: 277–296.PubMedCrossRefGoogle Scholar
  13. 13.
    Palay SL, Chan-Palay V. The Cerebellar Cortex, Cytology and Organization. New York: Springer-Verlag, 1974: 1–348.Google Scholar
  14. 14.
    Bayer SA, Altman J, Russo RJ, Zhang X. Timetables of neurogenesis in the human brain based on experimentally determined patterns in the rat. Neurotoxicol 1993; 14: 83–144.Google Scholar
  15. 15.
    Altman J, Bayer SA. Development of the Cerebellar System. Vol. 1,1st edn., 1997: 1–783.Google Scholar
  16. 16.
    Wingate RJ. The rhombic lip and early cerebellar development. Curr Opin Neurobiol 2001; 11: 82–88.PubMedCrossRefGoogle Scholar
  17. 17.
    Wechsler-Reya RJ, Scott MP. Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog. Neuron 1999; 22: 103–114.PubMedCrossRefGoogle Scholar
  18. 18.
    Altman J, Bayer SA. Prenatal development of the cerebellar system in the rat. I. Cytogenesis and histogenesis of the deep nuclei and the cortex of the cerebellum. J Comp Neurol 1978; 179: 23–48.PubMedCrossRefGoogle Scholar
  19. 19.
    Maricich SM, Gilmore EC, Herrup K. The role of tangential migration in the establishment of mammalian cortex. Neuron 2001; 31: 175–178.PubMedCrossRefGoogle Scholar
  20. 20.
    Wang VY, Zoghbi HY. Genetic regulation of cerebellar development. Nat Rev Neurosci 2001; 2: 484–491.PubMedCrossRefGoogle Scholar
  21. 21.
    Wingate RJ. The rhombic lip and early cerebellar development. Curr Opin Neurobiol 2001; 11: 82–88.PubMedCrossRefGoogle Scholar
  22. 22.
    Helms AW, Johnson JE. Progenitors of dorsal commissural interneurons are denned by MATH1 expression. Development 1998; 125: 919–928.PubMedGoogle Scholar
  23. 23.
    Ben-Arie N, Bellen HJ, Armstrong DL, McCall AE, Gordadze PR, Guo Q, et al. Mathl is essential for genesis of cerebellar granule neurons. Nature 1997; 390: 169–172.PubMedCrossRefGoogle Scholar
  24. 24.
    Hatten ME, Alder J, Zimmerman K, Heintz N. Genes involved in cerebellar cell specification and differentiation. Curr Opin Neurobiol 1997; 7: 40–47.PubMedCrossRefGoogle Scholar
  25. 25.
    Zhang L, Goldman JE. Generation of cerebellar interneurons from dividing precursors in white matter. Neuron 1996; 16: 47–54.PubMedCrossRefGoogle Scholar
  26. 26.
    Wingate RJ. The rhombic lip and early cerebellar development. Curr Opin Neurobiol 2001; 11: 82–88.PubMedCrossRefGoogle Scholar
  27. 27.
    Komuro H, Rakic P. Orchestration of neuronal migration by activity of ion channels, neurotransmitter receptors, and intracellular Ca2+ fluctuations. J Neurobiol 1998; 37: 110–130.PubMedCrossRefGoogle Scholar
  28. 28.
    Wood KA, Dipasquale B, Youle RJ. In situ labeling of granule cells for apoptosis-associated DNA fragmentation reveals different mechanisms of cell loss in developing cerebellum. Neuron 1993; 11: 621–632.PubMedCrossRefGoogle Scholar
  29. 29.
    Altman J, Bayer SA. Embryonic development of the rat cerebellum. III. Regional differences in the time of origin, migration, and settling of Purkinje cells. J Comp Neurol 1985; 231: 42–65.PubMedCrossRefGoogle Scholar
  30. 30.
    Altman J. Experimental reorganization of the cerebellar cortex. VII. Effects of late X-irradiation schedules that interfere with cell acquisition after stellate cells are formed. J Comp Neurol 1976; 165: 65–76.PubMedCrossRefGoogle Scholar
  31. 31.
    Ito M. The Cerebellum and Neural Control. New York: Raven Press, 1984.Google Scholar
  32. 32.
    Baptista CA, Hatten ME, Blazeski R, Mason CA. Cell-cell interactions influence survival and differentiation of purified Purkinje cells in vitro. Neuron 1994; 12: 243–260.PubMedCrossRefGoogle Scholar
  33. 33.
    Hauser KF, Gurwell JA, Turbek CS. Morphine inhibits Purkinje cell survival and dendritic differentiation in organotypic cultures of the mouse cerebellum. Exp Neurol 1994; 130: 95–105.PubMedCrossRefGoogle Scholar
  34. 34.
    Hauser KF, Stiene-Martin A. Opiates and the regulation of nervous system development: Evidence from in vitro studies. In: Hammer RP, Jr., editor. Neurobiology of Opiates. Boca Raton, Florida: CRC Press, 1993: 23–61.Google Scholar
  35. 35.
    Li Z, Lin H, Zhu Y, Wang M, Luo J. Disruption of cell cycle kinetics and cyclin-dependent kinase system by ethanol in cultured cerebellar granule progenitors. Dev Brain Res 2001; 132: 47–58.CrossRefGoogle Scholar
  36. 36.
    Miller MW. Migration of cortical neurons is altered by gestational exposure to ethanol. Alcohol Clin Exp Res 1993; 17: 304–314.PubMedCrossRefGoogle Scholar
  37. 37.
    Miller MW. Effects of alcohol on the generation and migration of cerebral cortical neurons. Science 1986; 233: 1308–1311.PubMedCrossRefGoogle Scholar
  38. 38.
    Gruol DL, Ryabinin AE, Parsons KL, Cole M, Wilson MC, Qiu Z. Neonatal alcohol exposure reduces NMDA induced Ca2+ signaling in developing cerebellar granule neurons. Brain Res 1998; 793: 12–20.PubMedCrossRefGoogle Scholar
  39. 39.
    Przewlocki R, Parsons KL, Sweeney DD, Trotter C, Netzeband JG, Siggins GR, et al. Opioid enhancement of calcium oscillations and burst events involving NMDA receptors and Ltype calcium channels in cultured hippocampal neurons. J Neurosci 1999; 19: 9705–9715.PubMedGoogle Scholar
  40. 40.
    Bearer CF, Swick AR, O’Riordan MA, Cheng G. Ethanol inhibits L1-mediated neurite outgrowth in postnatal rat cerebellar granule cells. J Biol Chem 1999; 274: 13264–13270.PubMedCrossRefGoogle Scholar
  41. 41.
    Burden-Gulley SM, Pendergast M, Lemmon V. The role of cell adhesion molecule L1 in axonal extension, growth cone motility, and signal transduction. Cell Tissue Res 1997; 290: 415–422.PubMedCrossRefGoogle Scholar
  42. 42.
    Komuro H, Rakic P. Intracellular Ca2+ fluctuations modulate the rate of neuronal migration. Neuron 1996; 17: 275–285.PubMedCrossRefGoogle Scholar
  43. 43.
    Komuro H, Rakic P. Dynamics of granule cell migration: a confocal microscopic study in acute cerebellar slice preparations. J Neurosci 1995; 15: 1110–1120.PubMedGoogle Scholar
  44. 44.
    Liesi P. Ethanol-exposed central neurons fail to migrate and undergo apoptosis. J Neurosci Res 1997; 48: 439–448.PubMedCrossRefGoogle Scholar
  45. 45.
    Pantazis NJ, Dohrman DP, Luo J, Thomas JD, Goodlett CR, West JR. NMDA prevents alcohol-induced neuronal cell death of cerebellar granule cells in culture. Alcohol Clin Exp Res 1995; 19: 846–853.PubMedCrossRefGoogle Scholar
  46. 46.
    West JR, Chen WJ, Pantazis NJ. Fetal alcohol syndrome: the vulnerability of the developing brain and possible mechanisms of damage. Metab Brain Dis 1994; 9: 291–322.PubMedCrossRefGoogle Scholar
  47. 47.
    West JR. Acute and long-term changes in the cerebellum following developmental exposure to ethanol. Alcohol Alcohol Suppl 1993; 2: 199–202.Google Scholar
  48. 48.
    Pantazis NJ, West JR, Dai D. The nitric oxide-cyclic GMP pathway plays an essential role in both promoting cell survival of cerebellar granule cells in culture and protecting the cells against ethanol neurotoxicity. J Neurochem 1998; 70: 1826–1838.PubMedGoogle Scholar
  49. 49.
    Oberdoerster J, Rabin RA. Enhanced caspase activity during ethanol-induced apoptosis in rat cerebellar granule cells. Eur J Pharmacol 1999; 385: 273–282.PubMedCrossRefGoogle Scholar
  50. 50.
    Bhave SV, Snell LD, Tabakoff B, Hoffman PL. Chronic ethanol exposure attenuates the anti-apoptotic effect of NMDA in cerebellar granule neurons. J Neurochem 2000; 75: 1035–1044.PubMedCrossRefGoogle Scholar
  51. 51.
    Borges S, Lewis PD. Effects of ethanol on postnatal cell acquisition in the rat cerebellum. Brain Res 1983; 271: 388–391.PubMedCrossRefGoogle Scholar
  52. 52.
    Zhang FX, Rubin R, Rooney TA. N-Methyl-D-aspartate inhibits apoptosis through activation of phosphatidylinositol 3-kinase in cerebellar granule neurons. A role for insulin receptor substrate-1 in the neurotrophic action of n-methyl-D-aspartate and its inhibition by ethanol. J Biol Chem 1998; 273: 26596–26602.PubMedCrossRefGoogle Scholar
  53. 53.
    Snell LD, Bhave SV, Tabakoff B, Hoffman PL. Chronic ethanol exposure delays the ‘developmental switch’ of the NMDA receptor 2A and 2B subunits in cultured cerebellar granule neurons. J Neurochem 2001; 78: 396–405.PubMedCrossRefGoogle Scholar
  54. 54.
    Hoffman PL, Iorio KR, Snell LD, Tabakoff B. Attenuation of glutamate-induced neurotoxicity in chronically ethanol-exposed cerebellar granule cells by NMDA receptor antagonists and ganglioside GM1. Alcohol Clin Exp Res 1995; 19: 721–726.PubMedCrossRefGoogle Scholar
  55. 55.
    Akinshola BE, Stewart RR, Karvonen LL, Taylor RE, Liesi P. Involvement of non-NMDA receptors in the rescue of weaver cerebellar granule neurons and sensitivity to ethanol of cerebellar AMPA receptors in oocytes. Mol Brain Res 2001; 93: 8–17.PubMedCrossRefGoogle Scholar
  56. 56.
    Valenzuela CF, Bhave S, Hoffman P, Harris RA. Acute effects of ethanol on pharmacologically isolated kainate receptors in cerebellar granule neurons: comparison with NMDA and AMPA receptors. J Neurochem 1998; 71: 1777–1780.PubMedGoogle Scholar
  57. 57.
    Littleton J, Little H. Current concepts of ethanol dependence. Addiction 1994; 89: 1397–1412.PubMedCrossRefGoogle Scholar
  58. 58.
    Hsiao SH, West JR, Mahoney JC, Frye GD. Postnatal ethanol exposure blunts upregulation of GABAA receptor currents in Purkinje neurons. Brain Res 1999; 832: 124–135.PubMedCrossRefGoogle Scholar
  59. 59.
    Hsiao SH, Parrish A, Nahm S, Abbott L, McCool B, Frye G. Effects of early postnatal ethanol intubation on GABAergic synaptic proteins. Dev Brain Res 2002; 138: 177–185.CrossRefGoogle Scholar
  60. 60.
    Ikonomidou C, Bittigau P, Ishimaru MJ, Wozniak DF, Koch C, Genz K, et al. Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome [see comments]. Science 2000; 287: 1056–1060.PubMedCrossRefGoogle Scholar
  61. 61.
    Littleton JM, Lovinger D, Liljequist S, Ticku R, Matsumoto I, Barron S. Role of polyamines and NMDA receptors in ethanol dependence and withdrawal. Alcohol Clin Exp Res 2001; 25: 132S-136S.PubMedGoogle Scholar
  62. 62.
    Cebers G, Hou YN, Cebere A, Terenius L, Liljequist S. Chronic ethanol enhances NMDA-induced AP-1 activity in cultured rat cerebellar granule cells. Neuroreport 1996; 8: 217–220.PubMedCrossRefGoogle Scholar
  63. 63.
    Cebers G, Cebere A, Zharkovsky A, Liljequist S. Glycine does not reverse the inhibitory actions of ethanol on NMDA receptor functions in cerebellar granule cells. Naunyn Schmiedebergs Arch Pharmacol 1996; 354: 736–745.PubMedCrossRefGoogle Scholar
  64. 64.
    Ben-Ari Y, Khazipov R, Leinekugel X, Caillard O, Gaiarsa JL. GABAA, NMDA and AMPA receptors: a developmentally regulated ‘menage a trois’. Trends Neurosci 1997; 20: 523–529.PubMedCrossRefGoogle Scholar
  65. 65.
    de la Monte SM, Neely TR, Cannon J, Wands JR. Ethanol impairs insulin-stimulated mitochondrial function in cerebellar granule neurons. Cell Mol Life Sci 2001; 58: 1950–1960.PubMedCrossRefGoogle Scholar
  66. 66.
    Vaudry D, Rousselle C, Basille M, Falluel-Morel A, Pamantung TF, Fontaine M, et al. Pituitary adenylate cyclase-activating polypeptide protects rat cerebellar granule neurons against ethanol-induced apoptotic cell death. Proc Natl Acad Sci USA 2002; 99: 6398–6403.PubMedCrossRefGoogle Scholar
  67. 67.
    Hallak H, Sciler AE, Green JS, Henderson A, Ross BN, Rubin R. Inhibition of insulin-like growth factor-I signaling by ethanol in neuronal cells. Alcohol Clin Exp Res 2001; 25: 1058–1064.PubMedCrossRefGoogle Scholar
  68. 68.
    Zhang FX, Rubin R, Rooney TA. Ethanol induces apoptosis in cerebellar granule neurons by inhibiting insulin-like growth factor 1 signaling. J Neurochem 1998; 71: 196–204.PubMedCrossRefGoogle Scholar
  69. 69.
    Bhave SV, Ghoda L, Hoffman PL. Brain-derived neurotrophic factor mediates the anti-apoptotic effect of NMDA in cerebellar granule neurons: signal transduction cascades and site of ethanol action. J Neurosci 1999; 19: 3277–3286.PubMedGoogle Scholar
  70. 70.
    Light KE, Brown DP, Newton BW, Belcher SM, Kane CJ. Ethanol-induced alterations of neurotrophin receptor expression on Purkinje cells in the neonatal rat cerebellum. Brain Res 2002; 924: 71–81.PubMedCrossRefGoogle Scholar
  71. 71.
    Light KE, Ge Y, Belcher SM. Early postnatal ethanol exposure selectively decreases BDNF and truncated TrkB-T2 receptor mRNA expression in the rat cerebellum. Mol Brain Res 2001; 93: 46–55.PubMedCrossRefGoogle Scholar
  72. 72.
    Heaton MB, Madorsky I, Paiva M, Mayer J. Influence of ethanol on neonatal cerebellum of BDNF gene-deleted animals: analyses of effects on Purkinje cells, apoptosis-related proteins, and endogenous antioxidants. J Neurobiol 2002; 51: 160–176.PubMedCrossRefGoogle Scholar
  73. 73.
    Luo J, West JR, Pantazis NJ. Nerve growth factor and basic fibroblast growth factor protect rat cerebellar granule cells in culture against ethanol-induced cell death. Alcohol Clin Exp Res 1997; 21: 1108–1120.PubMedGoogle Scholar
  74. 74.
    Chen WJ, Parnell SE, West JR. Neonatal alcohol and nicotine exposure limits brain growth and depletes cerebellar Purkinje cells. Alcohol 1998; 15: 33–41.PubMedCrossRefGoogle Scholar
  75. 75.
    McAlhany RE, Jr, West JR, Miranda RC. Glial-derived neurotrophic factor rescues calbindin-D28k-immunoreactive neurons in alcohol-treated cerebellar expiant cultures. J Neurobiol 1997; 33: 835–847.PubMedCrossRefGoogle Scholar
  76. 76.
    Luo J, Miller MW. Growth factor-mediated neural proliferation: target of ethanol toxicity. Brain Res Rev 1998; 27: 157–167.PubMedCrossRefGoogle Scholar
  77. 77.
    Di Chiara G, Acquas E, Tanda G. Ethanol as a neurochemical surrogate of conventional reinforcers: the dopamine-opioid link. Alcohol 1996; 13: 13–17.PubMedCrossRefGoogle Scholar
  78. 78.
    Fitzgerald LW, Nestler EJ. Molecular and cellular adaptations in signal transduction pathways following ethanol exposure. Clin Neurosci 1995; 3: 165–173.PubMedGoogle Scholar
  79. 79.
    Koob GF, Roberts AJ, Schulteis G, Parsons LH, Heyser CJ, Hyytia P, et al. Neurocircuitry targets in ethanol reward and dependence. Alcohol Clin Exp Res 1998; 22: 3–9.PubMedGoogle Scholar
  80. 80.
    Maier SE, Chen WJ, West JR. Prenatal binge-like alcohol exposure alters neurochemical profiles in fetal rat brain. Pharmacol Biochem Behav 1996; 55: 521–529.PubMedCrossRefGoogle Scholar
  81. 81.
    Guerri C, Renau-Piqueras J. Alcohol, astroglia, and brain development. Mol Neurobiol 1997; 15: 65–81.PubMedCrossRefGoogle Scholar
  82. 82.
    Aschner M, Allen JW. Astrocytes in methylmercury, ammonia, methionine sulfoximine and alcohol-induced neurotoxicity. Neurotoxicology 2000; 21: 573–579.PubMedGoogle Scholar
  83. 83.
    Rintala J, Jaatinen P, Kiianmaa K, Riikonen J, Kemppainen O, Sarviharju M, et al. Dose-dependent decrease in glial fibrillary acidic protein-immunoreactivity in rat cerebellum after lifelong ethanol consumption. Alcohol 2001; 23: 1–8.PubMedCrossRefGoogle Scholar
  84. 84.
    Dlugos CA, Pentney RJ. Quantitative immunocytochemistry of glia in the cerebellar cortex of old ethanol-fed rats. Alcohol 2001; 23: 63–69.PubMedCrossRefGoogle Scholar
  85. 85.
    Fadda F, Rossetti ZL. Chronic ethanol consumption: from neuroadaptation to neurodegeneration. Prog Neurobiol 1998; 56: 385–431.PubMedCrossRefGoogle Scholar
  86. 86.
    Guerri C. Neuroanatomical and neurophysiological mechanisms involved in central nervous system dysfunctions induced by prenatal alcohol exposure. Alcohol Clin Exp Res 1998; 22: 304–312.PubMedCrossRefGoogle Scholar
  87. 87.
    Crofford M, Smith AA. Growth retardation in young mice treated with dl-methadone. Science 1973; 181: 947–949.PubMedCrossRefGoogle Scholar
  88. 88.
    Hauser KF, McLaughlin PJ, Zagon IS. Endogenous opioid systems and the regulation of dendritic growth and spine formation. J Comp Neurol 1989; 281: 13–22.PubMedCrossRefGoogle Scholar
  89. 89.
    Hauser KF, Stiene-Martin A. Characterization of opioiddependent glial development in dissociated and organotypic cultures of mouse central nervous system: critical periods and target specificity. Dev Brain Res 1991; 62: 245–255.CrossRefGoogle Scholar
  90. 90.
    Hauser KF. Morphine regulates DNA synthesis in cerebellar neuroblasts in vitro. Dev Brain Res 1992; 70: 291–297.CrossRefGoogle Scholar
  91. 91.
    Hammer RP, Jr., Hauser KF. Consequences of early exposure to opioids on cell proliferation and neuronal morphogenesis. In: Miller M, editor. Development of the Central Nervous System: Effects of Alcohol and Opiates. New York: Wiley-Liss, 1992: 319–339.Google Scholar
  92. 92.
    Hauser KF, Houdi AA, Turbek CS, Elde RP, Maxson W, III. Opioids intrinsically inhibit the genesis of mouse cerebellar granule cell precursors in vitro: Differential impact of μ and δ receptor activation on proliferation and neurite elongation. Eur J Neurosci 2000; 12: 1281–1293.PubMedCrossRefGoogle Scholar
  93. 93.
    Zagon IS, McLaughlin PJ. Increased brain size and cellular content in infant rats treated with an opioid antagonist. Science 1983; 221: 1179–1180.PubMedCrossRefGoogle Scholar
  94. 94.
    Akil H, Watson SJ, Young E, Lewis ME, Khachaturian H, Walker JM. Endogenous opioids: biology and function. Ann Rev Neurosci 1984; 7: 223–255.PubMedCrossRefGoogle Scholar
  95. 95.
    Leslie FM, Chen Y, Winzer-Serhan UH. Opioid receptor and peptide mRNA expression in proliferative zones of fetal rat central nervous system. Can J Physiol Pharmacol 1998; 76: 284–293.PubMedCrossRefGoogle Scholar
  96. 96.
    Osborne JG, Kindy MS, Spruce BA, Hauser KF. Ontogeny of proenkephalin mRNA and enkephalin peptide expression in the cerebellar cortex of the rat: spatial and temporal patterns of expression follow maturational gradients in the external granular layer and in Purkinje cells. Dev Brain Res 1993; 76: 1–12.CrossRefGoogle Scholar
  97. 97.
    Zagon IS, Rhodes RE, McLaughlin PJ. Distribution of enkephalin immunoreactivity in germinative cells of developing rat cerebellum. Science 1985; 227: 1049–1051.PubMedCrossRefGoogle Scholar
  98. 98.
    Zagon IS, Gibo DM, McLaughlin PJ. Zeta (ξ), a growth-related opioid receptor in developing rat cerebellum: identification and characterization. Brain Res 1991; 551: 28–35.PubMedCrossRefGoogle Scholar
  99. 99.
    Hauser KF, Osborne JG, Stiene-Martin A, Meiner MH. Cellular localization of proenkephalin mRNA and enkephalin peptide products in cultured astrocytes. Brain Res 1990; 522: 347–353.PubMedCrossRefGoogle Scholar
  100. 100.
    Spruce BA, Curtis R, Wilkin GP, Glover DM. A neuropeptide precursor in cerebellum: proenkephalin exists in subpopulations of both neurons and astrocytes. EMBO J 1990; 9: 1787–1795.PubMedGoogle Scholar
  101. 101.
    Shinoda H, Marini AM, Cosi C, Schwartz JP. Brain region and gene specificity of neuropeptide gene expression in cultured astrocytes. Science 1989; 245: 415–417.PubMedCrossRefGoogle Scholar
  102. 102.
    Stiene-Martin A, Osborne JG, Hauser KF. Co-localization of proenkephalin mRNA using cRNA probes and a cell-type-specific marker for intact astrocytes in vitro. J Neurosci Methods 1991; 36: 119–126.PubMedCrossRefGoogle Scholar
  103. 103.
    Zhu Y, Hsu MS, Pintar JE. Developmental expression of the mu, kappa, and delta opioid receptor mRNAs in mouse. J Neurosci 1998; 18: 2538–2549.PubMedGoogle Scholar
  104. 104.
    Goldstein A. Binding selectivity profiles for ligands of multiple receptor types: focus on opioid receptors. Trends Pharmacol Sci 1987; 8: 456–459.CrossRefGoogle Scholar
  105. 105.
    Zagon IS, McLaughlin PJ. Opioid antagonist (naltrexone) modulation of cerebellar development: histological and morphometric studies. J Neurosci 1986; 6: 1424–1432.PubMedGoogle Scholar
  106. 106.
    Hauser KF, McLaughlin PJ, Zagon IS. Endogenous opioids regulate dendritic growth and spine formation in developing rat brain. Brain Res 1987; 416: 157–161.PubMedCrossRefGoogle Scholar
  107. 107.
    Vernadakis A, Estin C, Gibson DA, Amott S. Effects of methadone on ornithine decarboxylase and cyclic nucleotide phosphohydrolase in neuronal and glial cell cultures. J Neurosci Res 1982; 7: 111–117.PubMedCrossRefGoogle Scholar
  108. 108.
    Sakellaridis N, Vernadakis A. An unconventional response of adenylate cyclase to morphine and naloxone in the chicken during early development. Proc Natl Acad Sci USA 1986; 83: 2738–2742.PubMedCrossRefGoogle Scholar
  109. 109.
    Kornblum HI, Loughlin SE, Leslie FM. Effects of morphine on DNA synthesis in neonatal rat brain. Dev Brain Res 1987; 31: 45–52.CrossRefGoogle Scholar
  110. 110.
    Hammer RP, Jr. Effects of opioids on the developing brain. In: Hammer RP, Jr., editor. The Neurobiology of Opiates. Boca Raton, Florida: CRC Press, 1993: 1–21.Google Scholar
  111. 111.
    Bartolome JV, Alicke B, Bartolome MB. Central administration of morphine inhibits brain and liver ornithine decarboxylase activity in neonatal rats: involvement of transcription- and non-transcription-dependent mechanisms. Eur J Pharmacol 1997; 331: 145–153.PubMedCrossRefGoogle Scholar
  112. 112.
    Mangoura D. mu-Opioids activate tyrosine kinase focal adhesion kinase and regulate cortical cytoskeleton proteins cortactin and vinculin in chick embryonic neurons. J Neurosci Res 1997; 50: 391–401.PubMedCrossRefGoogle Scholar
  113. 113.
    Slotkin T. Perinatal exposure to methadone: how do early biochemical alterations cause neurofunctional disturbances? Prog Brain Res 1988; 73: 265–279.PubMedCrossRefGoogle Scholar
  114. 114.
    Schmahl W, Funk R, Miaskowski U, Plendl J. Long-lasting effects of naltrexone, an opioid receptor antagonist, on cell proliferation in developing rat forebrain. Brain Res 1989; 486: 297–300.PubMedCrossRefGoogle Scholar
  115. 115.
    Steele WJ, Johannesson T. Effects of prenatally-administered morphine on brain development and resultant tolerance to the analgesic effect of morphine in offspring of morphine treated rats. Acta Pharmacol Toxicol 1975; 36: 243–256.Google Scholar
  116. 116.
    Hammer RP, Jr., Ricalde AA, Seatriz JV. Effects of opiates on brain development. Neurotoxicol 1989; 10: 475–484.Google Scholar
  117. 117.
    Seatriz JV, Hammer RP, Jr. Effects of opiates on neuronal development in the rat cerebral cortex. Brain Res Bull 1993; 30: 523–527.PubMedCrossRefGoogle Scholar
  118. 118.
    Lorber BA, Freitag SK, Bartolome JV. Effects of beta-endorphin on DNA synthesis in brain regions of preweanling rats. Brain Res 1990; 531: 329–332.PubMedCrossRefGoogle Scholar
  119. 119.
    Zagon IS, McLaughlin PJ. Endogenous opioid systems regulate cell proliferation in the developing rat brain. Brain Res 1987; 412: 68–72.PubMedCrossRefGoogle Scholar
  120. 120.
    Hauser KF, Mangoura D. Diversity of the endogenous opioid system in development: novel signal transduction translates multiple extracellular signals into neural cell growth and differentiation. Perspect Dev Neurobiol 1998; 5: 437–449.PubMedGoogle Scholar
  121. 121.
    Knapp PE, Maderspach K, Hauser KF. Endogenous opioid system in developing normal and jimpy oligodendrocytes: ξ and κ opioid receptors mediate differential mitogenic and growth responses. Glia 1998; 22: 189–201.PubMedCrossRefGoogle Scholar
  122. 122.
    Gurwell JA, Hauser KF. Morphine does not affect astrocyte survival in developing primary mixed-glial cultures. Dev Brain Res 1993; 76: 293–298.CrossRefGoogle Scholar
  123. 123.
    Stiene-Martin A, Zhou R, Hauser KF. Regional, developmental, and cell cycle-dependent differences in ξ, δ, and κ, opioid receptor expression among cultured mouse astrocytes. Glia 1998; 22: 249–259.PubMedCrossRefGoogle Scholar
  124. 124.
    Oehmichen M, Meissner C, Reiter A, Birkholz M. Neuropathology in non-human immunodeficiency virus-infected drug addicts: hypoxic brain damage after chronic intravenous drug abuse. Acta Neuropathol (Berl) 1996; 91: 642–646.CrossRefGoogle Scholar
  125. 125.
    Kriegstein AR, Armitage BA, Kim PY. Heroin inhalation and progressive spongiform leukoencephalopathy. N Engl J Med 1997; 336: 589–590.PubMedCrossRefGoogle Scholar
  126. 126.
    Kriegstein AR, Shungu DC, Millar WS, Armitage BA, Brust JC, Chillrud S, et al. Leukoencephalopathy and raised brain lactate from heroin vapor inhalation (“chasing the dragon”). Neurology 1999; 53: 1765–1773.PubMedGoogle Scholar
  127. 127.
    Strang J, Griffiths P, Gossop M. Heroin smoking by ‘chasing the dragon’: origins and history. Addiction 1997; 92: 673–683.PubMedCrossRefGoogle Scholar
  128. 128.
    Gossop M, Griffiths P, Strang J. Chasing the dragon: characteristics of heroin chasers. Br J Addict 1988; 83: 1159–1162.PubMedCrossRefGoogle Scholar
  129. 129.
    Wolters EC, van Wijngaarden GK, Stam FC, Rengelink H, Lousberg RJ, Schipper ME, et al. Leucoencephalopathy after inhaling “heroin” pyrolysate. Lancet 1982; 2: 1233–1237.PubMedCrossRefGoogle Scholar
  130. 130.
    Kinney HC, White WF. Opioid receptors localize to the external granular cell layer of the developing human cerebellum. Neuroscience 1991; 45: 13–21.PubMedCrossRefGoogle Scholar
  131. 131.
    Zagon IS, Verderame MF, McLaughlin PJ. The biology of the opioid growth factor receptor (OGFr). Brain Res Rev 2002; 38: 351–376.PubMedCrossRefGoogle Scholar
  132. 132.
    Coyle JT, Pert CB. Ontogenetic development of [3H]naloxone binding in rat brain. Neuropharmacol 1976; 15: 555–560.CrossRefGoogle Scholar
  133. 133.
    Mansour A, Fox CA, Burke S, Meng F, Thompson RC, Akil H, et al. Mu, delta, and kappa opioid receptor mRNA expression in the rat CNS: An in situ hybridization study. J Comp Neurol 1994; 350: 412–438.PubMedCrossRefGoogle Scholar
  134. 134.
    Abeyta A, Dettmer TS, Barnes A, Vega D, Carta M, Gallegos N, et al. Delta opioid receptor localization in the rat cerebellum. Brain Res 2002; 931: 100–105.PubMedCrossRefGoogle Scholar
  135. 135.
    Platzer S, Winkler A, Schadrack J, Dworzak D, Tolle TR, Zieglgansberger W, et al. Autoradiographic distribution of mu-, delta- and kappa 1-opioid stimulated [35S]guanylyl-5′-O-(gamma-thio)-triphosphate binding in human frontal cortex and cerebellum. Neurosci Lett 2000; 283: 213–216.PubMedCrossRefGoogle Scholar
  136. 136.
    Schadrack J, Willoch F, Platzer S, Bartenstein P, Mahal B, Dworzak D, et al. Opioid receptors in the human cerebellum: evidence from [11C]diprenorphine PET, mRNA expression and autoradiography. Neuroreport 1999; 10: 619–624.PubMedCrossRefGoogle Scholar
  137. 137.
    Zagon IS, McLaughlin PJ. Morphine and brain growth retardation in the rat. Pharmacol 1977; 15: 276–282.Google Scholar
  138. 138.
    Zagon IS, McLaughlin PJ. Methadone and brain development. Experientia 1977; 33: 1486–1487.PubMedCrossRefGoogle Scholar
  139. 139.
    Willson NJ, Schneider JF, Roizin L, Fleiss JF, Rivers W, Demartini JE. Effects of methadone HC1 on the growth of organotypic cerebellar cultures prepared from methadone tolerant and control rats. J Pharmacol Exp Ther 1976; 199: 368–374.PubMedGoogle Scholar
  140. 140.
    King JS, Ho RH, Bishop GA. Anatomical evidence for enkephalin immunoreactive climbing fibres in the cerebellar cortex of the opossum. J Neurocytol 1986; 15: 545–559.PubMedCrossRefGoogle Scholar
  141. 141.
    Schulman JA, Finger TE, Brecha NC, Karten HJ. Enkephalin immunoreactivity in Golgi cells and mossy fibres of mammalian, avian, amphibian and teleost cerebellum. Neurosci 1981; 6: 2407–2416.CrossRefGoogle Scholar
  142. 142.
    Vathy I, Rimanoczy A, Eaton RC, Katay L. Sex dimorphic alterations in postnatal brain catecholamines after gestational morphine. Brain Res Bull 1995; 36: 185–193.PubMedCrossRefGoogle Scholar
  143. 143.
    Barg J, Belcheva MM, Zimlichman R, Levy R, Saya D, Mchale RJ, et al. Opioids inhibit endothelin-mediated DNA synthesis, phosphoinositide turnover, and Ca2+ mobilization in rat C6 glioma cells. J Neurosci 1994; 14: 5858–5864.PubMedGoogle Scholar
  144. 144.
    Knapp PE, Hauser KF. μ-Opioid receptor activation enhances DNA synthesis in immature oligodendrocytes. Brain Res 1996; 743: 341–345.PubMedCrossRefGoogle Scholar
  145. 145.
    Hauser KF, Stiene-Martin A, Mattson MP, Elde RP, Ryan SE, Godleske CC. μ-Opioid receptor-induced Ca2+ mobilization and astroglial development: Morphine inhibits DNA synthesis and stimulates cellular hypertrophy through a Ca2+-dependent mechanism. Brain Res 1996; 720: 191–203.PubMedCrossRefGoogle Scholar
  146. 146.
    Mangoura D, Sogos V, Dawson G. Protein kinase C-epsilon is a developmentally regulated, neuronal isoform in the chick embryo central nervous system. J Neurosci Res 1993; 35: 488–498.PubMedCrossRefGoogle Scholar
  147. 147.
    Bohn LM, Belcheva MM, Coscia CJ. Mitogenic signaling via endogenous kappa-opioid receptors in C6 glioma cells: evidence for the involvement of protein kinase C and the mitogen-activated protein kinase signaling cascade. J Neurochem 2000; 74: 564–573.PubMedCrossRefGoogle Scholar
  148. 148.
    Belcheva MM, Szucs M, Wang D, Sadee W, Coscia CJ. mu-Opioid receptor-mediated ERK activation involves calmodulindependent epidermal growth factor receptor transactivation. J Biol Chem 2001; 276: 33847–33853.PubMedCrossRefGoogle Scholar
  149. 149.
    Barg J, Belcheva MM, Coscia CJ. Evidence for the implication of phosphoinositol signal transduction in μ-opioid inhibition of DNA synthesis. J Neurochem 1992; 59: 1145–1152.PubMedCrossRefGoogle Scholar
  150. 150.
    Huang L-YM. Cellular mechanisms of excitatory and inhibitory actions of opioids. In: Tseng LF, editor. The Pharmacology of Opioid Peptides. 1st edn. London: Harwood Academic Publishers, 1995: 131–149.Google Scholar
  151. 151.
    Barg J, Belcheva M, McHale R, Levy R, Vogel Z, Coscia CJ. Betaendorphin is a potent inhibitor of thymidine incorporation into DNA via mu- and kappa-opioid receptors in fetal rat brain cell aggregates in culture. J Neurochem 1993; 60: 765–767.PubMedCrossRefGoogle Scholar
  152. 152.
    Polakiewicz RD, Schieferl SM, Gingras AC, Sonenberg N, Comb MJ. mu-Opioid receptor activates signaling pathways implicated in cell survival and translational control. J Biol Chem 1998; 273: 23534–23541.PubMedCrossRefGoogle Scholar
  153. 153.
    Law PY, Bergsbaken C. Properties of delta opioid receptor in neuroblastoma NS20Y: receptor activation and neuroblastoma proliferation. J Pharmacol Exp Ther 1995; 272: 322–332.PubMedGoogle Scholar
  154. 154.
    Lee YS, Wurster RD. Differential effects of methionine enkephalin on the growth of brain tumor cells. J Neurooncol 1994; 19: 11–15.PubMedCrossRefGoogle Scholar
  155. 155.
    Opanashuk LA, Hauser KF. Opposing actions of the EGF family and opioids: heparin binding-epidermal growth factor (HB-EGF) protects mouse cerebellar neuroblasts against the antiproliferative effect of morphine. Brain Res 1998; 804 87–94.PubMedCrossRefGoogle Scholar
  156. 156.
    Bohn LM, Belcheva MM, Coscia CJ. Mu-opioid agonist inhibition of kappa-opioid receptor-stimulated extracellular signal-regulated kinase phosphorylation is dynamin-dependent in C6 glioma cells. J Neurochem 2000; 74: 574–581.PubMedCrossRefGoogle Scholar
  157. 157.
    Jordan B, Devi LA. Molecular mechanisms of opioid receptor signal transduction. Br J Anaesth 1998; 81: 12–19.PubMedGoogle Scholar
  158. 158.
    Gomes I, Jordan BA, Gupta A, Trapaidze N, Nagy V, Devi LA. Heterodimerization of mu and delta opioid receptors: a role in opiate synergy. J Neurosci 2000; 20: RC110: 1–5.Google Scholar
  159. 159.
    Jordan BA, Trapaidze N, Gomes I, Nivarthi R, Devi LA. Oligomerization of opioid receptors with beta 2-adrenergic receptors: a role in trafficking and mitogen-activated protein kinase activation. Proc Natl Acad Sci USA 2001; 98: 343–348.PubMedCrossRefGoogle Scholar
  160. 160.
    Knapp PE, Itkis OS, Zhang L, Spruce BA, Hauser KF. Endogenous opioids and oligodendroglial function: possible autocrine/paracrine effects on cell survival and development. Glia 2001; 35: 156–165.PubMedCrossRefGoogle Scholar
  161. 161.
    Stiene-Martin A, Knapp PE, Martin KM, Gurwell JA, Ryan S, Thornton SR, et al. Opioid system diversity in developing neurons, astroglia, and oligodendroglia in the subventricular zone and striatum: impact on gliogenesis in vivo. Glia 2001; 36: 78–88.PubMedCrossRefGoogle Scholar
  162. 162.
    Gould E, Butcher LL. Transient expression of choline acetyltransferase-like immunoreactivity in Purkinje cells of the developing rat cerebellum. Brain Res 1987; 431: 303–306.PubMedGoogle Scholar
  163. 163.
    Clos J, Ghandour S, Eberhart R, Vincendon G, Gombos G. The cholinergic system in developing cerebellum: comparative study of normal, hypothyroid and underfed rats. Dev Neurosci 1989; 11: 188–204.PubMedCrossRefGoogle Scholar
  164. 164.
    Perry EK, Court JA, Johnson M, Smith CJ, James V, Cheng AV, et al. Autoradiographic comparison of cholinergic and other transmitter receptors in the normal human hippocampus. Hippocampus 1993; 3: 307–315.PubMedCrossRefGoogle Scholar
  165. 165.
    Court JA, Perry EK, Spurden D, Griffiths M, Kerwin JM, Morris CM, et al. The role of the cholinergic system in the development of the human cerebellum. Dev Brain Res 1995; 90: 159–167.CrossRefGoogle Scholar
  166. 166.
    Brooksbank BW, Walker D, Balazs R, Jorgensen OS. Neuronal maturation in the foetal brain in Down’s syndrome. Early Hum Dev 1989; 18: 237–246.PubMedCrossRefGoogle Scholar
  167. 167.
    Court JA, Perry EK, Spurden D, Griffiths M, Kerwin JM, Morris CM, et al. The role of the cholinergic system in the development of the human cerebellum. Dev Brain Res 1995; 90: 159–167.CrossRefGoogle Scholar
  168. 168.
    Jaarsma D, Ruigrok TJ, Caffe R, Cozzari C, Levey AI, Mugnaini E, et al. Cholinergic innervation and receptors in the cerebellum. Prog Brain Res 1997; 114: 67–96.PubMedGoogle Scholar
  169. 169.
    Airman J. Postnatal development of the cerebellar cortex in the rat. III. Maturation of the components of the granular layer. J Comp Neurol 1972; 145: 465–514.CrossRefGoogle Scholar
  170. 170.
    Boegman RJ, Parent A, Hawkes R. Zonation in the rat cerebellar cortex: patches of high acetylcholinesterase activity in the granular layer are congruent with Purkinje cell compartments. Brain Res 1988; 448: 237–251.PubMedCrossRefGoogle Scholar
  171. 171.
    Role LW, Berg DK. Nicotinic receptors in the development and modulation of CNS synapses. Neuron 1996; 16: 1077–1085.PubMedCrossRefGoogle Scholar
  172. 172.
    Alkondon M, Pereira EF, Cortes WS, Maelicke A, Albuquerque EX. Choline is a selective agonist of alpha7 nicotinic acetylcholine receptors in the rat brain neurons. Eur J Neurosci 1997; 9: 2734–2742.PubMedCrossRefGoogle Scholar
  173. 173.
    Albuquerque EX, Alkondon M, Pereira EF, Castro NG, Schrattenholz A, Barbosa CT, et al. Properties of neuronal nicotinic acetylcholine receptors: pharmacological characterization and modulation of synaptic function. J Pharmacol Exp Ther 1997; 280: 1117–1136.PubMedGoogle Scholar
  174. 174.
    Albuquerque EX, Pereira EF, Alkondon M, Schrattenholz A, Maelicke A. Nicotinic acetylcholine receptors on hippocampal neurons: distribution on the neuronal surface and modulation of receptor activity. J Recept Signal Transduct Res 1997; 17: 243–266.PubMedGoogle Scholar
  175. 175.
    Zoli M, Le NN, Hill JAJ, Changeux JP. Developmental regulation of nicotinic ACh receptor subunit mRNAs in the rat central and peripheral nervous systems. J Neurosci 1995; 15: 1912–1939.PubMedGoogle Scholar
  176. 176.
    Tice MA, Hashemi T, Taylor LA, McQuade RD. Distribution of muscarinic receptor subtypes in rat brain from postnatal to old age. Dev Brain Res 1996; 92: 70–76.CrossRefGoogle Scholar
  177. 177.
    Winzer-Serhan UH, Leslie FM. Codistribution of nicotinic acetylcholine receptor subunit alpha3 and beta4 mRNAs during rat brain development. J Comp Neurol 1997; 386: 540–554.PubMedCrossRefGoogle Scholar
  178. 178.
    Kinney HC, O’Donnell TJ, Kriger P, White WF. Early developmental changes in [3H]nicotine binding in the human brainstem. Neuroscience 1993; 55: 1127–1138.PubMedCrossRefGoogle Scholar
  179. 179.
    Morley BJ. The embryonic and post-natal expression of the nicotinic receptor alpha 3-subunit in rat lower brainstem. Mol Brain Res 1997; 48: 407–412.PubMedCrossRefGoogle Scholar
  180. 180.
    Opanashuk LA, Pauly JR, Hauser KF. Effect of nicotine on cerebellar granule neuron development. Eur J Neurosci 2001; 13: 48–56.PubMedCrossRefGoogle Scholar
  181. 181.
    Dominguez del Toro E, Juiz JM, Smillie FI, Lindstrom J, Criado M. Expression of alpha 7 neuronal nicotinic receptors during postnatal development of the rat cerebellum. Dev Brain Res 1997; 98: 125–133.CrossRefGoogle Scholar
  182. 182.
    Didier M, Berman SA, Lindstrom J, Bursztajn S. Characterization of nicotinic acetylcholine receptors expressed in primary cultures of cerebellar granule cells. Mol Brain Res 1995; 30: 17–28.PubMedCrossRefGoogle Scholar
  183. 183.
    De Filippi G, Baldwinson T, Sher E. Evidence for nicotinic acetylcholine receptor activation in rat cerebellar slices. Pharmacol Biochem Behav 2001; 70: 447–455.PubMedCrossRefGoogle Scholar
  184. 184.
    Caruncho HJ, Guidotti A, Lindstrom J, Costa E, Pesold C. Subcellular localization of the alpha 7 nicotinic receptor in rat cerebellar granule cell layer. Neuroreport 1997; 8: 1431–1433.PubMedCrossRefGoogle Scholar
  185. 185.
    Kawa K. Acute synaptic modulation by nicotinic agonists in developing cerebellar Purkinje cells of the rat. J Physiol 2002; 538: 87–102.PubMedCrossRefGoogle Scholar
  186. 186.
    Navarro HA, Scidler FJ, Eylers JP, Baker FE, Dobbins SS, Lappi SE, et al. Effects of prenatal nicotine exposure on development of central and peripheral cholinergic neurotransmitter systems. Evidence for cholinergic trophic influences in developing brain. J Pharmacol Exp Ther 1989; 251: 894–900.PubMedGoogle Scholar
  187. 187.
    McFarland BJ, Scidler FJ, Slotkin TA. Inhibition of DNA synthesis in neonatal rat brain regions caused by acute nicotine administration. Dev Brain Res 1991; 58: 223–229.CrossRefGoogle Scholar
  188. 188.
    Slotkin TA, Lappi SE, Scidler FJ. Impact of fetal nicotine exposure on development of rat brain regions: critical sensitive periods or effects of withdrawal? Brain Res Bull 1993; 31: 319–328.PubMedCrossRefGoogle Scholar
  189. 189.
    Roy TS, Andrews JE, Scidler FJ, Slotkin TA. Nicotine evokes cell death in embryonic rat brain during neurulation. J Pharmacol Exp Ther 1998; 287 1136–1144.PubMedGoogle Scholar
  190. 190.
    Lee M, Martin-Ruiz C, Graham A, Court J, Jaros E, Perry R, et al. Nicotinic receptor abnormalities in the cerebellar cortex in autism. Brain 2002; 125: 1483–1495.PubMedCrossRefGoogle Scholar
  191. 191.
    Gao W-Q, Heintz N, Hatten ME. Cerebellar granule cell neurogenesis is regulated by cell-cell interactions in vitro. Neuron 1991; 6: 705–715.PubMedCrossRefGoogle Scholar
  192. 192.
    Prendergast MA, Harris BR, Mayer S, Holley RC, Hauser KF, Littleton JM. Chronic nicotine exposure reduces N-methyl-D-aspartate receptor-mediated damage in the hippocampus without altering calcium accumulation or extrusion: evidence for calbindin-D28K overexpression. Neuroscience 2001; 102: 75–85.PubMedCrossRefGoogle Scholar
  193. 193.
    Berger F, Gage FH, Vijayaraghavan S. Nicotinic receptor-induced apoptotic cell death of hippocampal progenitor cells. J Neurosci 1998; 18: 6871–6881.PubMedGoogle Scholar
  194. 194.
    Delbono O, Gopalakrishnan M, Renganathan M, Monteggia LM, Messi ML, Sullivan JP. Activation of the recombinant human alpha 7 nicotinic acetylcholine receptor significantly raises intracellular free calcium. J Pharmacol Exp Ther 1997; 280: 428–438.PubMedGoogle Scholar
  195. 195.
    Villablanca AC. Nicotine stimulates DNA synthesis and proliferation in vascular endothelial cells in vitro. J Appl Physiol 1998; 84: 2089–2098.PubMedGoogle Scholar
  196. 196.
    Yan GM, Lin SZ, Irwin RP, Paul SM. Activation of muscarinic cholinergic receptors blocks apoptosis of cultured cerebellar granule neurons. Mol Pharmacol 1995; 47: 248–257.PubMedGoogle Scholar
  197. 197.
    Wong RO. Cholinergic regulation of [Ca2+]i during cell division and differentiation in the mammalian retina. J Neurosci 1995; 15: 2696–2706.PubMedGoogle Scholar
  198. 198.
    Rakowicz-Szulczynska EM, Mclntosh DG, Smith M. Growth factor-mediated mechanisms of nicotine-dependent carcinogenesis. Carcinogenesis 1994; 15: 1839–1846.PubMedCrossRefGoogle Scholar
  199. 199.
    Rakowicz-Szulczynska EM, Mclntosh DG, Perry M, Smith ML. PDGF AA as mediator in nicotine-dependent carcinogenesis. Carcinogenesis 1996; 17: 1813–1818.PubMedCrossRefGoogle Scholar
  200. 200.
    Jang MH, Shin MC, Jung SB, Lee TH, Bahn GH, Kwon YK, et al. Alcohol and nicotine reduce cell proliferation and enhance apoptosis in dentate gyrus. Neuroreport 2002; 13: 1509–1513.PubMedCrossRefGoogle Scholar
  201. 201.
    Abrous DN, Adriani W, Montaron MF, Aurousseau C, Rougon G, Le Moal M, et al. Nicotine self-administration impairs hippocampal plasticity. J Neurosci 2002; 22: 3656–3662.PubMedGoogle Scholar
  202. 202.
    Dajas-Bailador FA, Soliakov L, Wonnacott S. Nicotine activates the extracellular signal-regulated kinase 1/2 via the alpha7 nicotinic acetylcholine receptor and protein kinase A, in SH-SY5Y cells and hippocampal neurones. J Neurochem 2002; 80: 520–530.PubMedCrossRefGoogle Scholar
  203. 203.
    Dempsey DA, Benowitz NL. Risks and benefits of nicotine to aid smoking cessation in pregnancy. Drug Saf 2001; 24: 277–322.PubMedCrossRefGoogle Scholar
  204. 204.
    Pantazis NJ, Dohrman DP, Goodlett CR, Cook RT, West JR. Vulnerability of cerebellar granule cells to alcohol-induced cell death diminishes with time in culture. Alcohol Clin Exp Res 1993; 17: 1014–1021.PubMedCrossRefGoogle Scholar
  205. 205.
    Bonthius D, Tzouras G, Karacay B, Mahoney J, Hutton A, McKim R, et al. Deficiency of neuronal nitric oxide synthase (nNOS) worsens alcohol-induced microencephaly and neuronal loss in developing mice. Dev Brain Res 2002; 138: 45–59.CrossRefGoogle Scholar
  206. 206.
    Srivastava N, Vernadakis A. Maturation of cerebellar granule cells is delayed in cultures derived from ethanol-treated chick embryos: survival and proliferation studies. Int J Dev Neurosci 1995; 13: 529–537.PubMedCrossRefGoogle Scholar
  207. 207.
    Gruol DL, Parsons KL. Chronic alcohol reduces calcium signaling elicited by glutamate receptor stimulation in developing cerebellar neurons. Brain Res 1996; 728: 166–174.PubMedCrossRefGoogle Scholar
  208. 208.
    West JR, Parnell SE, Chen WJ, Cudd TA. Alcohol-mediated Purkinje cell loss in the absence of hypoxemia during the third trimester in an ovine model system. Alcohol Clin Exp Res 2001; 25: 1051–1057.PubMedCrossRefGoogle Scholar
  209. 209.
    Bauer-Moffett C, Airman J. The effect of ethanol chronically administered to preweanling rats on cerebellar development: a morphological study. Brain Res 1977; 119: 249–268.PubMedCrossRefGoogle Scholar
  210. 210.
    Thomas JD, Goodlett CR, West JR. Alcohol-induced Purkinje cell loss depends on developmental timing of alcohol exposure and correlates with motor performance. Dev Brain Res 1998; 105: 159–166.CrossRefGoogle Scholar
  211. 211.
    Lim DK, Park SH, Choi WJ. Subacute nicotine exposure in cultured cerebellar cells increased the release and uptake of glutamate. Arch Pharm Res 2000; 23: 488–494.PubMedGoogle Scholar
  212. 212.
    Jaarsma D, Dino MR, Cozzari C, Mugnaini E. Cerebellar choline acetyltransferase positive mossy fibres and their granule and unipolar brush cell targets: a model for central cholinergic nicotinic neurotransmission. J Neurocytol 1996; 25: 829–842.PubMedCrossRefGoogle Scholar
  213. 213.
    Freund RK, Palmer MR. Ethanol depression of cerebellar Purkinje neuron firing involves nicotinic acetylcholine receptors. Exp Neurol 1997; 143: 319–322.PubMedCrossRefGoogle Scholar
  214. 214.
    de la Garza R, McGuire TJ, Freedman R, Hoffer BJ. Nicotineinduced inhibition of cerebellar Purkinje neurons: specific actions of nicotine and selective blockade by mecamylamine. Neuropharmacology 1989; 28: 495–501.PubMedCrossRefGoogle Scholar
  215. 215.
    de la Garza R, McGuire TJ, Freedman R, Hoffer BJ. The electrophysiological effects of nicotine in the rat cerebellum: evidence for direct postsynaptic actions. Neurosci Lett 1987; 80: 303–308.PubMedCrossRefGoogle Scholar
  216. 216.
    Agulhon C, Charnay Y, Vallet P, Abitbol M, Kobetz A, Bertrand D, et al. Distribution of mRNA for the alpha4 subunit of the nicotinic acetylcholine receptor in the human fetal brain. Mol Brain Res 1998; 58: 123–131.PubMedCrossRefGoogle Scholar
  217. 217.
    Yang X, Criswell HE, Breese GR. Action of ethanol on responses to nicotine from cerebellar Purkinje neurons: relationship to methyllycaconitine (MLA) inhibition of nicotine responses. Neurochem Int 1999; 35: 185–194.PubMedCrossRefGoogle Scholar

Copyright information

© Taylor & Francis 2003

Authors and Affiliations

  • Kurt F. Hauser
    • 1
    • 4
  • Valeriya K. Khurdayan
    • 1
  • Robin J. Goody
    • 1
  • Avindra Nath
    • 2
    • 3
  • Alois Saria
    • 5
  • James R. Pauly
    • 6
  1. 1.Department of Anatomy & NeurobiologyUniversity of Kentucky College of MedicineLexingtonUSA
  2. 2.Department of Microbiology & ImmunologyUniversity of Kentucky College of MedicineLexingtonUSA
  3. 3.Department of NeurologyUniversity of Kentucky College of MedicineLexingtonUSA
  4. 4.The Markey Cancer CenterUniversity of Kentucky College of MedicineLexingtonUSA
  5. 5.Division of NeurochemistryDepartment of PsychiatryInnsbruckAustria
  6. 6.College of PharmacyUniversity of Kentucky Medical CenterLexingtonUSA
  7. 7.Department of NeurologyJohns Hopkins UniversityBaltimoreUSA

Personalised recommendations