Cocaine-induced inhibition of process outgrowth in locus coeruleus neurons: role of gestational exposure period and offspring sex

Abstract

Cocaine use during pregnancy is associated with neurobehavioral problems in school-aged children that implicate alterations in attentional processes, potentially due to impairments in the noradrenergic system. We analyzed locus coeruleus (LC) neurite outgrowth characteristics following the administration of a physiologically relevant dose of cocaine (3.0mg/kg) issued during critical phases of gestation (gestational day (GD)8–14, GD15–21, GD8–21). Results showed that cocaine inhibits LC neurite outgrowth and development, as evidenced by a decrease in total neurite length, a decrease in neurite length per cell, and a decrease in the percentage of cells with neurites. Morphological differences between cultures treated with and without cocaine were also evident. Further, the specific gestational exposure period effects were also dependent upon sex of the fetus. Finally, a discriminant function anaylsis suggested that the pattern and magnitude of alterations that defined the GD8–14 exposure were significantly different from that of the GD15–21 or GD8–21 exposures. Collectively, these data demonstrate a direct, disruptive effect of cocaine on noradrenergic neurons and may provide a neurobiological basis for changes in attentional function seen in offspring exposed to cocaine in utero.