Rodriguez V M, Mendoza-Trejo M S, Hernandez-Plata I, Giordano M
Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla 3001, Juriquilla, Qro, 76230, Mexico.
Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla 3001, Juriquilla, Qro, 76230, Mexico.
Neurotoxicology. 2017 Jan;58:161-170. doi: 10.1016/j.neuro.2016.12.006. Epub 2016 Dec 21.
Atrazine (ATR) is an herbicide broadly used in the world to control weeds in corn and sorghum fields, and it is potentially toxic for the dopaminergic system. Alterations in dopaminergic markers after ATR administration in rats and C57BL/6 mice have been reported. Behaviorally, it has been observed that ATR exposure causes hypoactivity shortly after its administration. To understand how acute ATR administration induces hypoactivity, we set out to map the brain areas responsive to ATR using c-Fos as a marker of neuronal activity, and tyrosine hydroxylase (TH) as a marker of dopaminergic neurons. The levels of glutamate and gamma-aminobutyric acid (GABA) were measured using high performance liquid chromatography, and spontaneous locomotor activity was evaluated as well. Male Sprague-Dawley rats received a systemic injection of 1% methyl cellulose (vehicle) or 100mg ATR/kg body weight to evaluate locomotor activity immediately after injection, c-Fos and TH immunohistochemistry in forebrain, midbrain and hindbrain, or glutamate and GABA content in various brain areas 90min after injection. To assess the possible involvement of the GABAergic system on ATR effects we tested the effects of a GABA-B antagonist. We found statistically significant decreases in locomotor activity, which were partially reversed by the GABA-B antagonist, and increases in the number of c-Fos-positive cells in thalamus, central amygdala, subthalamic nucleus, superior colliculus, and substantia nigra, TH positive cells were not selectively activated by ATR. The acute administration of ATR did not affect GABA or glutamate tissue levels but significantly decreased locomotor activity. These results corroborate the hypoactivity-inducing effect of ATR, and show that non-dopaminergic cells respond to the acute administration of ATR. The activation of cell populations in the basal ganglia and their target nuclei may contribute to the acute behavioral effects of ATR.
阿特拉津（ATR）是一种在全球广泛用于控制玉米和高粱田杂草的除草剂，它对多巴胺能系统具有潜在毒性。已有报道称，在大鼠和C57BL/6小鼠中给予ATR后，多巴胺能标志物会发生改变。在行为方面，已观察到ATR暴露在给药后不久会导致活动减少。为了了解急性给予ATR如何诱导活动减少，我们着手使用c-Fos作为神经元活动的标志物，酪氨酸羟化酶（TH）作为多巴胺能神经元的标志物，来绘制对ATR有反应的脑区图谱。使用高效液相色谱法测量谷氨酸和γ-氨基丁酸（GABA）的水平，并评估自发运动活动。雄性Sprague-Dawley大鼠接受全身注射1%甲基纤维素（载体）或100mg ATR/kg体重，以在注射后立即评估运动活动，在注射后90分钟评估前脑、中脑和后脑的c-Fos和TH免疫组织化学，或各个脑区的谷氨酸和GABA含量。为了评估GABA能系统对ATR效应的可能参与，我们测试了GABA-B拮抗剂的作用。我们发现运动活动有统计学意义的降低，GABA-B拮抗剂部分逆转了这种降低，并且丘脑、中央杏仁核、丘脑底核、上丘和黑质中c-Fos阳性细胞数量增加，TH阳性细胞未被ATR选择性激活。急性给予ATR不影响GABA或谷氨酸组织水平，但显著降低运动活动。这些结果证实了ATR诱导活动减少的作用，并表明非多巴胺能细胞对急性给予ATR有反应。基底神经节及其靶核中细胞群的激活可能导致ATR急性行为效应。
