PRENATAL COCAINE EXPOSURE DISRUPTS THE DEVELOPMENT OF THE SEROTONERGIC SYSTEM
PRENATAL COCAINE EXPOSURE DISRUPTS THE DEVELOPMENT OF THE SEROTONERGIC SYSTEM
复制标题
DOI：
10.1016/0006-8993(92)90450-n
复制
发表时间：
1992-02-14
期刊：
影响因子：
2.9
通讯作者：
AZMITIA, EC
中科院分区：
文献类型：
--
作者：
AKBARI, HM;KRAMER, HK;AZMITIA, EC
在临床和实验室研究中，已发现产前可卡因暴露导致许多神经行为异常。我们先前已经证明，可卡因抑制培养中发育中的5-羟色胺神经元的生长。本研究探讨了可卡因对体内5-羟色胺系统发育的影响。将妊娠大鼠注射可卡因（40 mg/kg s.c.）从妊娠第13天到分娩。一组大鼠在出生后第1-5天额外注射可卡因（10 mg/kg s.c.）。[H-3]帕罗西汀是5-羟色胺摄取载体的选择性配体，用于定量出生后1天、1周和4周的5-羟色胺终末纤维密度。在出生后一天和一周，发现暴露于可卡因显著降低[H-3]帕罗西汀标记的位点，从而降低皮质和海马中5-羟色胺纤维的密度。到出生后四周，没有观察到明显的影响，表明已经恢复。一个月时进行的血清素免疫细胞化学显示皮质中的纤维分布正常，但CA 1和CA 2海马区的纤维丢失。产后治疗减轻了产前可卡因暴露的影响，导致[H-3]帕罗西汀结合水平在一周内与生理盐水对照组相当，在皮质中甚至高于生理盐水对照组。我们的结论是，可卡因延迟成熟的血清素系统时，产前管理，但可能会加速成熟时，产前和产后管理。
Prenatal cocaine exposure has been found to result in a number of neurobehavioral abnormalities in both clinical and laboratory studies. We have previously shown that cocaine inhibits the growth of developing serotonin neurons in culture. This study examines the effects of cocaine on the developing serotonin system in vivo. Pregnant rats were injected with cocaine (40 mg/kg s.c.) from gestational day 13 to parturition. One group of rats was additionally injected on postnatal days 1-5 with cocaine (10 mg/kg s.c.). [H-3]Paroxetine, selective ligand for the serotonin uptake carrier, was used to quantify serotonin terminal fiber density at one day, one week, and four weeks postnatal. Cocaine exposure was found to significantly decrease [H-3]paroxetine-labelled sites and thus the density of serotonin fibers in the cortex and hippocampus at one day and one week postnatal. By four weeks postnatal, no significant effect was observed, indicating that a recovery had occurred. Serotonin immunocytochemistry performed at one month revealed normal fiber distribution in the cortex but a loss of fibers in the CA1 and CA2 hippocampal fields. Postnatal treatment alleviated the effects of prenatal cocaine exposure, resulting in [H-3]paroxetine binding levels at one week which were comparable to and, in the cortex, even higher than those of saline controls. We conclude that cocaine delays the maturation of the serotonin system when administered prenatally but may accelerate maturation when administered both pre- and postnatally.