Effects of maternal oral administration of morphine sulfate on developing rat fetal cerebrum: A morphometrical evaluation

Abstract

Intrauterine morphine exposure is a risk factor for neurological and behavioral deficit in children, although the precise underlying biological correlate for this is unclear. Female pregnant rats were orally treated with 0.1 mg/ml of morphine solution on the 21st day of gestation. Pregnant rats were killed on the 21st day of gestation and their fetuses were taken out and evaluated for growth and cerebral development. The fetuses were fixed and followed by dehydration through graded ethanol solutions and were then embedded and their heads were coronally sectioned through the frontal cerebral cortex. Quantitative computer-assisted morphometric study was done on the frontal cerebral cortex (FCC) which consists of cortical plate (CP), intermediate (migratory) zone (IZ) and matrix (proliferative) zone (MZ) in the rat embryos. The results showed that morphine exposure caused a significant reduction of fetal weight and crown-to-rump length in morphine exposure group. The present study showed that animals with intrauterine morphine exposure, induced by a period of reduced placental blood flow during the second week of pregnancy, demonstrate reduced both cortical thickness and the numbers of neurons in the developing fetal frontal cerebral cortex (FCC). Histomorphometric evaluation revealed that the thickness of the CP was significantly decreased in the morphine-exposed embryos. In addition, neuronal counting showed that cell proliferation in the CP was suppressed after morphine administration and that the migration of neurons from the matrix zone (MZ) to the cortex was decelerated. In conclusion, these results showed that morphine exposure during the second week of pregnancy could affect brain development in a way, which could lead to neurological and behavioral deficits in the postnatal animal.