Opioid system diversity in developing neurons, astroglia, and oligodendroglia in the subventricular zone and striatum: impact on gliogenesis in vivo

Glia. 2001 Oct;36(1):78-88.


Accumulating evidence, obtained largely in vitro, indicates that opioids regulate the genesis of neurons and glia and their precursors in the nervous system. Despite this evidence, few studies have assessed opioid receptor expression in identified cells within germinal zones or examined opioid effects on gliogenesis in vivo. To address this question, the role of opioids was explored in the subventricular zone (SVZ) and/or striatum of 2-5-day-old and/or adult ICR mice. The results showed that subpopulations of neurons, astrocytes, and oligodendrocytes in the SVZ and striatum differentially express mu-, delta-, and/or kappa-receptor immunoreactivity in a cell type-specific and developmentally regulated manner. In addition, DNA synthesis was assessed by examining 5-bromo-2'-deoxyuridine (BrdU) incorporation into glial and nonglial precursors. Morphine (a preferential mu-agonist) significantly decreased the number of BrdU-labeled GFAP(+) cells compared with controls or mice co-treated with naltrexone plus morphine. Alternatively, in S100beta(+) cells, morphine did not significantly decrease BrdU incorporation; however, significant differences were noted between mice treated with morphine and those treated with morphine plus naltrexone. Most cells were GFAP(-)/S100beta(-). When BrdU incorporation was assessed within the total population (glia and nonglia), morphine had no net effect, but naltrexone alone markedly increased BrdU incorporation. This finding suggests that DNA synthesis in GFAP(-)/S100beta(-) cells is tonically suppressed by endogenous opioids. Assuming that S100beta and GFAP, respectively, distinguish among younger and older astroglia, this implies that astroglial replication becomes increasingly sensitive to morphine during maturation, and suggests that opioids differentially regulate the development of distinct subpopulations of glia and glial precursors.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / physiology
  • Amino Acid Transport System X-AG / metabolism
  • Animals
  • Animals, Newborn / anatomy & histology
  • Animals, Newborn / growth & development
  • Animals, Newborn / metabolism
  • Antigens, Differentiation / metabolism
  • Antigens, Surface / metabolism
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Bromodeoxyuridine / pharmacokinetics
  • Calcium-Binding Proteins / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Division / drug effects
  • Cell Division / physiology*
  • Glial Fibrillary Acidic Protein / metabolism
  • Immunohistochemistry
  • Lateral Ventricles / cytology
  • Lateral Ventricles / growth & development*
  • Lateral Ventricles / metabolism
  • Mice
  • Mice, Inbred ICR / anatomy & histology
  • Mice, Inbred ICR / growth & development
  • Mice, Inbred ICR / metabolism
  • Morphine / pharmacology
  • Naltrexone / pharmacology
  • Neostriatum / cytology
  • Neostriatum / growth & development*
  • Neostriatum / metabolism
  • Nerve Growth Factors / metabolism
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Oligodendroglia / cytology
  • Oligodendroglia / drug effects
  • Oligodendroglia / metabolism*
  • Opioid Peptides / metabolism
  • Receptors, Opioid / drug effects
  • Receptors, Opioid / metabolism*
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins*


  • Amino Acid Transport System X-AG
  • Antigens, Differentiation
  • Antigens, Surface
  • Calcium-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • Nerve Growth Factors
  • Opioid Peptides
  • Receptors, Opioid
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins
  • oligodendrocyte O antigen, mouse
  • Naltrexone
  • Morphine
  • Bromodeoxyuridine