Transplacental cocaine exposure. 3: Mechanisms underlying altered brain development

摘要: In a mouse model of transplacental cocaine exposure we have demonstrated alterations in brain structure and function offspring including disturbances growth, disruption neocortical cytoarchitecture, transient as well persistent behavioral deficits. One mechanism by which may alter fetal development is through cocaine-induced alpha-adrenergic-mediated (uterine) arterial vasoconstriction. this study pregnant Swiss Webster (SW) mice were injected with HCl (20 or 40 mg/kg, SC) without any changes evident mean blood pressure (MAP) measurements. These physiology results suggest that our model, cocaine's effects on the fetus are not due to maternal vasoconstriction, nor concomitant hypoperfusion fetus. separate series experiments, SW dams administered at mg/kg/day (COC 40), 20 20), 10 10) [SC, divided two daily doses, from embryonic day (E) 8 E17 inclusive]. Additional groups cocaine-treated phentolamine (5 SC), short-acting alpha-adrenergic antagonist, 15 min prior each dose (Phent COC 40, Phent 20, 10). Animals born postnatal growth retardation deficits first-order conditioning P9 comparable dams, received same regimen injections pretreatment. Like offspring, also deficit blocking paradigm. The findings confirm extend data, imply rodent mechanisms (including vasoconstriction) unlikely mediate these toxic developing brain.