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围产期暴露于多氯联苯的成年Long-Evans大鼠中的可卡因致敏作用。

Cocaine sensitization in adult Long-Evans rats perinatally exposed to polychlorinated biphenyls.

作者信息

Miller Mellessa M, Sprowles Jenna L N, Voeller Jason N, Meyer Abby E, Sable Helen J K

机构信息

Department of Psychology, University of Memphis, Memphis, TN 38152, USA.

Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

出版信息

Neurotoxicol Teratol. 2017 Jul;62:34-41. doi: 10.1016/j.ntt.2017.04.005. Epub 2017 Apr 29.

Abstract

Polychlorinated biphenyls (PCBs) are ubiquitous environmental toxicants known to adversely affect the nervous system and more specifically the dopamine system. Developmental PCB exposure in rats has been shown to produce alterations in dopaminergic signaling that persist into adulthood. The reinforcing properties of psychostimulants are typically modulated via the dopaminergic system, so this project used a behavioral sensitization paradigm to evaluate whether perinatal PCB exposure altered sensitization to the psychostimulant cocaine. Long-Evans rats were perinatally exposed to 0, 3 or 6mg/kg/day of PCBs throughout gestation and lactation. One male and female pup from each litter was retained for behavioral testing. Both horizontal and vertical activity were used to measure cocaine sensitization following repeated injections of 10mg/kg cocaine (IP) on post-natal day (PND) 91-96 and again after a week in the home cage on PND 103. A final locomotor activity session following a challenge injection of 20mg/kg was given on PND 110 to further evaluate the availability of presynaptic dopamine stores. The PCB-exposed rats appeared to be pre-sensitized to cocaine as they exhibited a greater degree of cocaine-induced locomotor activation to the initial injections of cocaine and therefore demonstrated a more rapid onset of cocaine behavioral sensitization compared to non-exposed controls. These results add to the literature detailing how perinatal exposure to dopamine-disrupting contaminants can change the developing brain, thereby producing permanent changes in the neurobehavioral response to psychostimulants later in life.

摘要

多氯联苯(PCBs)是普遍存在的环境毒物,已知会对神经系统产生不利影响,更具体地说是对多巴胺系统产生影响。已表明,在大鼠发育过程中接触多氯联苯会导致多巴胺能信号传导发生改变,并持续到成年期。精神兴奋剂的强化特性通常通过多巴胺能系统进行调节,因此本项目采用行为敏化范式来评估围产期接触多氯联苯是否会改变对精神兴奋剂可卡因的敏化作用。在整个妊娠期和哺乳期,将Long-Evans大鼠围产期暴露于0、3或6mg/kg/天的多氯联苯中。每窝保留一只雄性和一只雌性幼崽用于行为测试。在出生后第91 - 96天重复注射10mg/kg可卡因(腹腔注射)后,以及在出生后第103天在家笼中饲养一周后,分别使用水平和垂直活动来测量可卡因敏化作用。在出生后第110天进行一次20mg/kg的激发注射后的最后一次运动活动实验,以进一步评估突触前多巴胺储备的可用性。与未接触多氯联苯的对照组相比,接触多氯联苯的大鼠似乎对可卡因预先致敏,因为它们在初次注射可卡因时表现出更大程度的可卡因诱导的运动激活,因此显示出可卡因行为敏化的发作更快。这些结果进一步丰富了相关文献,详细说明了围产期接触破坏多巴胺的污染物如何改变发育中的大脑,从而在生命后期对精神兴奋剂的神经行为反应产生永久性变化。

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