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

Accumulating evidence, obtained largely in vitro, indicates that opioids re gulate the genesis of neurons and glia and their precursors in the nervous system. Despite this evidence, few studies have assessed opioid receptor ex pression in identified cells within germinal zones or examined opioid effec ts on gliogenesis in vivo. To address this question, the role of opioids wa s 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, a strocytes, and oligodendrocytes in the SVZ and striatum differentially expr ess mu-, delta-, and/or kappa -receptor immunoreactivity in a cell type-spe cific and developmentally regulated manner. In addition, DNA synthesis was assessed by examining 5-bromo-2'-deoxyuridine (BrdU) incorporation into gli al and nonglial precursors. Morphine (a preferential mu -agonist) significa ntly decreased the number of BrdU-labeled GFAP(+) cells compared with contr ols or mice co-treated with naltrexone plus morphine. Alternatively, in S10 0 beta (+) cells, morphine did not significantly decrease BrdU incorporatio n; however, significant differences were noted between mice treated with mo rphine and those treated with morphine plus naltrexone. Most cells were GFA P(-)/S100 beta (-). When BrdU incorporation was assessed within the total p opulation (glia and nonglia), morphine had no net effect, but naltrexone al one markedly increased BrdU incorporation. This finding suggests that DNA s ynthesis in GFAP(-)/S100 beta (-) cells is tonically suppressed by endogeno us opioids. Assuming that S100 beta and GFAP, respectively, distinguish amo ng younger and older astroglia, this implies that astroglial replication be comes increasingly sensitive to morphine during maturation, and suggests th at opioids differentially regulate the development of distinct subpopulatio ns of glia and glial precursors. (C) 2001 Wiley-Liss, Inc.