ENDOGENOUS OPIOID SYSTEMS AND THE GROWTH OF OLIGODENDROCYTE PROGENITORS - PARADOXICAL INCREASES IN OLIGODENDROGENESIS AS AN INDIRECT MECHANISM OF OPIOID ACTION

Endogenous opioids inhibit nervous system development by inhibiting th e proliferation of certain neuronal and glial progenitors. To determin e whether opioids affect the growth of preoligodendrocytes, the effect s of the endogenous opioid [Met5]-enkephalin were examined in preoligo dendrocytes in primary mixed-glial and preoligodendrocyte-enriched (> 98% pure) cultures. Proliferating preoligodendrocytes in mixed-glial o r preoligodendrocyte-enriched cultures were continuously treated for a total of 40 h with either basal growth media (controls), 1 muM [Met5] -enkephalin, 1 muM [Met5]-enkephalin plus the opioid antagonist naloxo ne (3 muM), or naloxone alone (3 muM), and incubated in [H-3]-thymidin e (0.2 muCi/ml/4-6 h) after 34-36 h of opioid exposure. Opioid-depende nt changes in DNA synthesis were assessed autoradiographically in 04-i mmunoreactive oligodendrocyte progenitors. Naloxone alone significantl y decreased the rate of DNA synthesis and number of 04-immunoreactive preoligodendrocytes in mixed-glial cultures. However, naloxone and/or [Met5]-enkephalin did not affect DNA synthesis or the number of 04-imm unoreactive preoligodendrocytes in cultures enriched in preoligodendro cytes. The results suggest that astrocytes, or perhaps another cell ty pe, play a permissive role in opioid-dependent alterations in preoligo dendrocyte proliferation. Endogenous opioids affect the genesis of neu ral cells by both direct and indirect mechanisms. (C) 1993 Wiley-Liss, Inc.