Rodriguez Veronica M, Thiruchelvam Mona, Cory-Slechta Deborah A
Environmental and Occupational Health Sciences Institute, and Department of Environmental and Occupational Medicine, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854, USA.
Environ Health Perspect. 2005 Jun;113(6):708-15. doi: 10.1289/ehp.7783.
The widespread use of atrazine (ATR) and its persistence in the environment have resulted in documented human exposure. Alterations in hypothalamic catecholamines have been suggested as the mechanistic basis of the toxicity of ATR to hormonal systems in females and the reproductive tract in males. Because multiple catecholamine systems are present in the brain, however, ATR could have far broader effects than are currently understood. Catecholaminergic systems such as the two major long-length dopaminergic tracts of the central nervous system play key roles in mediating a wide array of critical behavioral functions. In this study we examined the hypothesis that ATR would adversely affect these brain dopaminergic systems. Male rats chronically exposed to 5 or 10 mg/kg ATR in the diet for 6 months exhibited persistent hyperactivity and altered behavioral responsivity to amphetamine. Moreover, when measured 2 weeks after the end of exposure, the levels of various monoamines and the numbers of tyrosine hydroxylase-positive (TH+) and -negative (TH-) cells measured using unbiased stereology were reduced in both dopaminergic tracts. Acute exposures to 100 or 200 mg/kg ATR given intraperitoneally to evaluate potential mechanisms reduced both basal and potassium-evoked striatal dopamine release. Collectively, these studies demonstrate that ATR can produce neurotoxicity in dopaminergic systems that are critical to the mediation of movement as well as cognition and executive function. Therefore, ATR may be an environmental risk factor contributing to dopaminergic system disorders, underscoring the need for further investigation of its mechanism(s) of action and corresponding assessment of its associated human health risks.
阿特拉津（ATR）的广泛使用及其在环境中的持久性已导致有记录的人类接触。下丘脑儿茶酚胺的改变被认为是ATR对女性激素系统和男性生殖道毒性的作用机制基础。然而，由于大脑中存在多个儿茶酚胺系统，ATR的影响可能远比目前所了解的更为广泛。儿茶酚胺能系统，如中枢神经系统的两条主要长程多巴胺能通路，在介导一系列关键行为功能中发挥着关键作用。在本研究中，我们检验了ATR会对这些脑多巴胺能系统产生不利影响的假设。雄性大鼠在饮食中慢性暴露于5或10 mg/kg ATR 6个月后，表现出持续的多动以及对苯丙胺的行为反应性改变。此外，在暴露结束2周后测量时，使用无偏倚立体学方法测得的两条多巴胺能通路中的各种单胺水平以及酪氨酸羟化酶阳性（TH+）和阴性（TH-）细胞数量均减少。腹腔注射100或200 mg/kg ATR进行急性暴露以评估潜在机制，结果显示基础和钾诱发的纹状体多巴胺释放均减少。总体而言，这些研究表明，ATR可在对运动以及认知和执行功能介导至关重要的多巴胺能系统中产生神经毒性。因此，ATR可能是导致多巴胺能系统紊乱的一个环境风险因素，这凸显了进一步研究其作用机制以及相应评估其相关人类健康风险的必要性。
