Opioids modulate cell division in the germinal zone of the late embryonic neocortex

Opioid effects on cell division in the embryonic cerebral cortex were exami ned using two experimental approaches: (i) the presence of opioid receptors in the embryonic day 16 mouse neocortex was tested using immunohistochemic al techniques; (ii) the values of the indices of [H-3]thymidine pulse label led cells and mitotic indices were estimated in the ventricular zone of the embryonic day 16 mouse neocortex 2.5, 4.5 and 8.5 h after administration t o pregnant females of selected opioid receptor agonists or the opioid antag onist naloxone. The immunohistochemical study demonstrated that distinct su bpopulations of the ventricular zone cells express mu, delta or kappa opioi d receptors. Acute exposure of mouse embryos to mu, delta and kappa opioid receptor agonists or naloxone differentially affects the indices of [H-3] t hymidine pulse labelled cells and mitotic indices indicating changes in the cell cycle composition. Treatment with the mu opioid receptor agonist D-Al a(2)-MePhe(4), Gly-ol(5)-enkephalin (DAGO), or the partially selective kapp a opioid receptor agonist bremazocine, increased the [H-3]thymidine labelli ng and mitotic indices. In contrast, the delta receptor agonist (D-Ser(8))- leucine enkephalin-Thr (DSLET) produced a decrease in the labelled cell ind ices and mitotic indices. Naloxone provided a biphasic effect: a decrease i n the values of labelled cell indices 2.5 h after naloxone administration, followed by an increase in the values of the indices at 4.5 and 8.5 h. Thes e results suggest that the endogenous embryonic/maternal opioid systems are involved in the regulation of cell division in the ventricular zone of the late embryonic cortex.