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

Abstract

Cocaine use during pregnancy is affiliated with neurobehavioral abnormalities in offspring that are associated with problems of attention. Given the putative role of the noradrenergic system in attentional processes, impairments in the noradrenergic system may underlie specific attentionally sensitive, neurobehavioral alterations. Recent data using a clinically relevant intravenous (iv) route of administration show that the norepinephrine cell bodies of the locus coeruleus (LC) are a primary target for in utero cocaine exposure. Cell survival and neurite outgrowth of LC neurons were studied using two paradigms: (1) in vitro, using a physiologically relevant concentration of cocaine, and (2) in vivo, using a clinically relevant intravenous rat model. Fetal cocaine exposure significantly decreased neuronal survival (in vitro: P=.0001, n=24; in vivo: P=.0337, n=30), reduced neurite initiation (in vitro: P=.001, n=24; in vivo: P=.0169, n=30), decreased the number 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 approach toward an understanding of noradrenergic neurons as they respond to cocaine during development suggest that cocaine may affect behavior by negatively regulating neuronal pathfinding and synaptic connectivity.