Gender-related differences in cocaine toxicity in the rat.
Gender-related differences in cocaine toxicity in the rat.
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发表时间：
1993-08
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通讯作者：
H. Morishima;Y. Abe;M. Matsuo;K. Akiba;T. Masaoka;T. Cooper
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作者：
H. Morishima;Y. Abe;M. Matsuo;K. Akiba;T. Masaoka;T. Cooper
为了检验我们的假设，即大鼠中可卡因毒性存在性别相关差异，将可卡因（2 mg/kg/min）长期插入导管的雄性大鼠和卵巢切除或完整的雌性大鼠中静脉注射，直到循环衰竭开始。观察到可卡因毒性的一系列表现，从轻微的中枢神经刺激到致命的心血管崩溃。在毒性体征或症状出现时抽取动脉血来测定可卡因浓度。雄性和卵巢切除大鼠产生心血管毒性表现所需的可卡因剂量和血浆浓度显着低于未绝育的雌性大鼠。血浆胆碱酯酶活性在雄性动物中最低，在完整雌性中最高。这些数据表明，可卡因的全身毒性在雄性大鼠中增强，因为诱导毒性体征和症状所需的剂量和血浆浓度较低。
To test our hypotheses that gender-related differences in cocaine toxicity exist in the rat, cocaine (2 mg/kg/min) was infused intravenously in chronically catheterized male and ovariectomized or intact female rats until the onset of circulatory collapse. Sequential manifestations of cocaine toxicity from mild central nervous stimulation to fatal cardiovascular collapse were observed. Arterial blood was withdrawn at the onset of the toxic signs or symptoms for determination of cocaine concentrations. Dosages and plasma concentrations of cocaine required to produce cardiovascular toxic manifestations were significantly lower in male and ovariectomized rats than in intact females. Plasma cholinesterase activity was lowest in the male animals and highest in intact females. These data suggest that systemic toxicity of cocaine is enhanced in male rats, because lower doses and plasma concentrations are required to induce toxic signs and symptoms.