PRENATAL COCAINE PRODUCES DEFICITS IN SEROTONIN MEDIATED NEUROENDOCRINE RESPONSES IN ADULT-RAT PROGENY - EVIDENCE FOR LONG-TERM FUNCTIONAL ALTERATIONS IN BRAIN-SEROTONIN PATHWAYS

被引:40
作者
CABRERA, TM [1 ]
YRACHETA, JM [1 ]
LI, Q [1 ]
LEVY, AD [1 ]
VANDEKAR, LD [1 ]
BATTAGLIA, G [1 ]
机构
[1] LOYOLA UNIV, STRITCH SCH MED, DEPT PHARMACOL, 2160 S 1ST AVE, MAYWOOD, IL 60153 USA
关键词
ACTH; CORTICOSTERONE; RENIN; PROLACTIN; SEROTONIN RECEPTORS; P-CHLOROAMPHETAMINE;
D O I
10.1002/syn.890150208
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (C) 1993 Wiley-Liss, Inc.
引用
收藏
页码:158 / 168
页数:11
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