Cocaine decreases cell survival and inhibits neurite extension of rat locus coeruleus neurons

Cocaine use during pregnancy is affiliated with neurobehavioral abnormaliti es in offspring that are associated with problems of attention. Given the p utative role of the noradrenergic system in attentional processes, impairme nts in the noradrenergic system may underlie specific attentionally sensiti ve, neurobehavioral alterations. Recent data using a clinically relevant in travenous (iv) route of administration show that the norepinephrine cell bo dies of the locus coeruleus (LC) are a primary target for in utero cocaine exposure. Cell survival and neurite outgrowth of LC neurons were studied us ing two paradigms: (1) in vitro, using a physiologically relevant concentra tion of cocaine, and (2) in vivo, using a clinically relevant intravenous r at model. Fetal cocaine exposure significantly decreased neuronal survival tin vitro: P=.0001, n = 24; in vivo: P=.0337, n = 30), reduced neurite init iation tin vitro: P=.001, n =24; in vivo: P=.0169, n = 30), decreased the n umber of neurites elaborated (in vivo: P=.0031, n = 30), and reduced total neurite length (in vivo: P=.0237, n = 30). The results of this novel approa ch toward an understanding of noradrenergic neurons as they respond to coca ine during development suggest that cocaine may affect behavior by negative ly regulating neuronal pathfinding and synaptic connectivity. (C) 2001 Else vier Science Inc. All rights reserved.