Prenatal cocaine produces deficits in serotonin mediated neuroendocrine responses in adult rat progeny: evidence for long-term functional alterations in brain serotonin pathways.
Cocaine produces biochemical alterations in brain serotonin (5-HT) neurons. Since 5-HT is critical to the development of fetal 5-HT neurons and target tissues, we hypothesized that in utero exposure to cocaine could result in long-term alterations in postnatal 5-HT systems. Pregnant Sprague-Dawley rats were administered either saline or (-)cocaine (15 mg/kg, s.c., b.i.d.) from gestational day 13 to 20. Prenatal cocaine exposure did not alter litter size, gender number, or progeny birth weights. Functional alterations in serotonergic systems were determined in postnatal day (PD) 70 male progeny by measuring changes in 5-HT mediated plasma hormones following a single 8 mg/kg injection of the 5-HT releaser p-chloroamphetamine (PCA). Cocaine exposed male progeny exhibited significant reductions in adrenocorticotropic hormone (ACTH, -43%) and renin (-62%) responses to PCA. However, no alterations were observed in the corticosterone or prolactin response to PCA. In utero exposure to cocaine did not alter basal levels of ACTH, renin, corticosterone, or prolactin. There were no significant differences in the density of either hypothalamic or cortical 5-HT uptake sites. Likewise, there were no significant differences in the densities of any of the 5-HT1 receptor subtypes or in the density of 5-HT2 receptors in cortex. These data, which provide the first demonstration of deficits in 5-HT mediated neuroendocrine function in adult progeny following in utero exposure to cocaine, indicate long-term functional alterations of brain 5-HT systems.
Cabrera
T M
TM
Department of Pharmacology, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois 60153.
Yracheta
J M
JM
Li
Q
Q
Levy
A D
AD
Van de Kar
L D
LD
Battaglia
G
G
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D005260:Female; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009490:Neurosecretory Systems / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011388:Prolactin / Q000097:blood; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012083:Renin / Q000097:blood; D012701:Serotonin / Q000502:physiology*; D010133:p-Chloroamphetamine / Q000494:pharmacology
D011985:Receptors, Serotonin; D012701:Serotonin; D010133:p-Chloroamphetamine; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D012083:Renin; D003042:Cocaine; D003345:Corticosterone