Research ReportEffects of maternal oral administration of morphine sulfate on developing rat fetal cerebrum: A morphometrical evaluation
Introduction
In recent years there has been increasing interest in the biologic effects of opiate abuse. Several studies have indicated that opiates such as morphine can be transferred from adult females to the central nervous system of developing offspring via placental transport and the maternal milk supply (Kirby, 1981). Cord blood sampling in humans and animals has shown that morphine rapidly crosses the placenta (Fisher and Patton, 2001). However, in the placental vasculature, morphine causes vasoconstriction potentially reducing blood flow through the placenta and subsequently to the fetus, by increasing vascular resistance (Tommaso, 2003). It is possible that maternal exposure to morphine during pregnancy could alter developmental process in the fetus (Siddiqui et al., 1995). Postmortem data on infants born to heroin addicts demonstrates that growth retardation is due mainly to a decrease in both size and number of cells in many organs (Levy and Koren, 1990). The prenatal exposure to opiate probably leads to disturbances in the development of the central nervous system (Chasnoff et al., 1980). Exposure to opiate drugs such as heroin and morphine during pregnancy has been associated with a variety of adverse effects that range from premature birth to fetal and neonatal death, chromosomal aberration, and decreased birth weight and growth retardation (Besunder and Blumer, 1990). In the rat, prenatal opiate exposure has effects parallel to those in the human, such as increased fetal and neonatal death and birth weight (Hans et al., 1984). In human morphine exposure during pregnancy results in general retardation of growth and development. A large proportion of infants born to morphine-addicted mothers are underweight and display disturbances in the development of the central nervous system (Heshman and Stitzer, 1989). Chronic morphine administration reduced the size of the dopamine neurons by an average of 25 percent (Sklair, 1996). Recently, opiates have been shown to promote apoptotic death of cells of the immune and nervous systems, DNA fragmentation in microglia and in neurons increased with higher morphine levels and longer exposure (Shxian, 1998). In addition, it has been shown that prenatal morphine exposure could cause neural tube deficiency in the mouse embryos (Nasiraei-Moghadama et al., 2005).
In this study, the neurotoxic effects of prenatal morphine exposure were evaluated by examining the neuronal count and thickness of frontal cerebral cortex in the rat embryos.
Section snippets
Results
No significant differences in indicators of embryotoxicity were found between the sham and control groups. Although no difference was observed in terms of maternal food or water consumption between the sham and control groups at either time point.
Discussion
It has been shown that exposure to opiate drugs such as heroin and morphine during pregnancy has been associated with premature birth, fetal and neonatal death, chromosomal aberrations, decreased birth weights and growth retardation (Besunder and Blumer, 1990). The present study confirmed that administration of morphine to pregnant mice resulted a significant reduction in mean of fetal weight and crown-to-rump length which agreed with previous data (Tao et al., 2001). This finding suggests that
Animals and morphine administration
Fifteen adult Sprague–Dawley female rats (Razy Institute, Tehran, Iran), 10–12 weeks old, weighting 230–250 g, were maintained under standard laboratory conditions. Animals were housed in an environment of 21 ± 0.5 °C with a relative humidity of 50 ± 10% and a 12-h light-dark cycle. Food and water were always available. To determine the day of estrus, females were daily placed with sexually vigorous studs for a brief observation. Estrus was determined by the occurrence of lordosis in response to
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