Developmental changes of H-3-labelled mu-opioid receptors in brainstems ofintra-uterine growth-restricted rats

The opioid CL-system is involved in brainstem-mediated respiratory control. Infants with intra-uterine growth restriction (IUGR) have more respiratory disorders in the early postnatal period. Using [H-3]DAGO, a mu -selective ligand, and a computer-based image analysis of autoradiography, we compared the ontogeny and distribution of Et-opioid binding sites in the brainstem of IUGR and control rats in utero (E21), at birth (P0) and on postnatal day s 1 (P1), P7, P10, P14 and P21. The ontogeny pattern was found to be simila r in both groups. The density of the binding sites, which was low in E21, i ncreased at P0, slightly declined at P1 and remained relatively constant th ereafter. The distribution of DAGO-binding sites, also similar in both grou ps, was heterogeneous and was much denser in the dorsal areas of medulla an d pens. In particular, binding sites were highly concentrated in nuclei inv olved in the cardio-respiratory function. However, DAGO-binding density was higher at all ages (except for P0 and P1) in IUGR than in control rats. Ta ken together, these results give at least a partial explanation for the eff ects of IUGR which lowers the Apgar score at birth and raises the incidence of respiratory disorders in infants. (C) 2001 Elsevier Science B.V. All ri ghts reserved.