Morishima H O, Abe Y, Matsuo M, Akiba K, Masaoka T, Cooper T B
Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York, NY.
J Lab Clin Med. 1993 Aug;122(2):157-63.
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 Arterial blood was withdrawn at the onset of the toxic signs or symptoms for determination of cocaine concentrations.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.
为了验证我们的假设，即大鼠存在可卡因毒性的性别相关差异，将可卡因（2毫克/千克/分钟）静脉输注到长期插管的雄性大鼠以及去卵巢或完整雌性大鼠体内，直至循环衰竭开始。观察到了可卡因毒性从轻度中枢神经刺激到致命心血管衰竭的一系列表现。在出现毒性体征或症状时抽取动脉血以测定可卡因浓度。产生心血管毒性表现所需的可卡因剂量和血浆浓度在雄性和去卵巢大鼠中显著低于完整雌性大鼠。雄性动物的血浆胆碱酯酶活性最低，完整雌性大鼠的最高。这些数据表明，雄性大鼠中可卡因的全身毒性增强，因为诱导毒性体征和症状所需的剂量和血浆浓度较低。
