Dey M S, Krieger R I, Ritter R C
Toxicol Appl Pharmacol. 1987 Feb;87(2):212-21. doi: 10.1016/0041-008x(87)90283-3.
Paraquat's (PQ) effect on feeding behavior in the rat was examined using a conditioned taste aversion (CTA) paradigm. CTA is a learned avoidance of tastes closely associated with prior illness. Male Sprague-Dawley rats trained to drink an instant breakfast solution were subsequently offered a novel-flavored solution and consumption was measured over 30 min. Following consumption of the novel solution, PQ (0.48-48.0 mumol/kg) was injected subcutaneously. Peak blood PQ concentrations were measured by serially sampling blood (0.15 ml) from an indwelling jugular cannula between 10 and 35 min after injection. Two days later, the rats were offered the same novel-flavored solution. Paraquat produced dose-dependent avoidance of the novel solution when injected subcutaneously. A PQ dosage of 2.7 mumol/kg or less did not alter consumption. The ED50 for CTA production of 13.0 mumol/kg was determined by log-probit analysis. The minimum effective dosage was 4.2 micron/kg. The doses examined did not produce overt clinical or histological signs of toxicity. Peak blood paraquat concentration was linearly related (r = 0.995) to dosage. Additionally when administered by gavage CTAs occurred only with a much larger PQ dosage (480 mumol/kg). Thermal lesions of a hindbrain circumventricular organ, the area postrema (AP), prevented PQ-induced CTAs despite repeated PQ injections. Additionally, weight loss following PQ exposure was also attenuated by AP lesions. CTAs were induced in these same AP-lesioned rats by oral administration of copper sulfate. This substance conditions taste aversions by activating vagal afferent neurons. The fact that copper sulfate-induced aversions were not blocked by lesions of the area posterema indicates that the lesioned rats are capable of forming CTAs when treated with a toxicant which does not act via the AP. These data indicate that PQ produces CTAs in a dose-dependent manner. Furthermore, PQ-induced CTAs and weight loss are mediated by the AP. The AP may contain receptors which detect xenobiotics, enabling animals to avoid future contact with these compounds.
使用条件性味觉厌恶（CTA）范式研究了百草枯（PQ）对大鼠进食行为的影响。CTA是一种对与先前疾病密切相关的味道的习得性回避。将雄性Sprague-Dawley大鼠训练饮用速溶早餐溶液，随后提供一种新口味溶液，并在30分钟内测量其消耗量。在消耗新溶液后，皮下注射PQ（0.48 - 48.0 μmol/kg）。在注射后10至35分钟之间，通过从留置的颈静脉插管中连续采集血液（0.15 ml）来测量血液中PQ的峰值浓度。两天后，给大鼠提供相同的新口味溶液。皮下注射百草枯会产生剂量依赖性的对新溶液的回避。2.7 μmol/kg或更低的PQ剂量不会改变消耗量。通过对数概率分析确定CTA产生的ED50为13.0 μmol/kg。最小有效剂量为4.2 μmol/kg。所检查的剂量未产生明显的临床或组织学毒性迹象。血液中百草枯峰值浓度与剂量呈线性相关（r = 0.995）。此外，当通过灌胃给药时，仅在大得多的PQ剂量（480 μmol/kg）下才会出现CTA。后脑室周器官即最后区（AP）的热损伤，尽管多次注射PQ，仍可防止PQ诱导的CTA。此外，AP损伤也减轻了PQ暴露后的体重减轻。通过口服硫酸铜在这些相同的AP损伤大鼠中诱导出CTA。该物质通过激活迷走神经传入神经元来形成味觉厌恶。硫酸铜诱导的厌恶未被最后区损伤所阻断这一事实表明，当用不通过AP起作用的毒物处理时，损伤大鼠能够形成CTA。这些数据表明PQ以剂量依赖性方式产生CTA。此外，PQ诱导的CTA和体重减轻是由AP介导的。AP可能含有检测异生物质的受体，使动物能够避免未来与这些化合物接触。
