MU-OPIOID RECEPTOR ACTIVATION ENHANCES DNA-SYNTHESIS IN IMMATURE OLIGODENDROCYTES

Opioids disrupt nervous system development by inhibiting the prolifera tion of neuronal and glial progenitors. These studies explored the hyp othesis that mu opioid receptors are expressed by immature oligodendro cytes (OLs) and are functionally related to growth. Antibodies identif ying the cloned mu opioid receptor demonstrated that cultured OLs expr essed mu opioid receptor immunoreactivity very early during developmen t. Cultures were treated with the selective mu opioid receptor agonist H-Tyr-Pro-Phe (N-Me)-D-Pro-NH2 (PL017; 1 mu M), or PL017 (1 mu M) plu s the antagonist naloxone (3 mu M). Opioid-dependent changes in DNA sy nthesis were assessed by determining the proportion of bromodeoxyuridi ne (BrdU)-labeled O4-immunoreactive OLs. Treatment with PL017 caused a 311% increase in the proportion of O4-immunoreactive OLs incorporatin g BrdU compared to untreated controls, and these effects were prevente d by co-administering naloxone. These preliminary results indicate tha t (i) immature OLs express mu opioid receptors and that (ii) the activ ation of this receptor type is functionally coupled to DNA synthesis a nd the cell division cycle. The expression of opioid receptors by OLs suggests that the endogenous opioid system is widely distributed among glial types.