Cocaine-induced inhibition of process outgrowth in locus coeruleus neurons: role of gestational exposure period and offspring sex.
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 (3.0 mg/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 analysis 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.
Snow
Diane M
DM
The University of Kentucky, Department of Anatomy and Neurobiology, Willard Medical Center-MN212, 800 Rose Street, Lexington, KY 40536-0298, USA. dsnow@uky.edu
Carman
Heidi M
HM
Smith
Jeffrey D
JD
Booze
Rosemarie M
RM
Welch
Marian A
MA
Mactutus
Charles F
CF
D000818:Animals; D000831:Animals, Newborn; D001288:Attention / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D007275:Injections, Intravenous; D008125:Locus Coeruleus / Q000166:cytology* / Q000187:drug effects*; D008297:Male; D008431:Maternal-Fetal Exchange / Q000502:physiology; D016501:Neurites / Q000187:drug effects* / Q000648:ultrastructure*; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D020318:Rats, Long-Evans; D012737:Sex Factors
D003042:Cocaine