Sex differences in (+)-amphetamine- and (+)-methamphetamine-induced behavioral response in male and female Sprague-Dawley rats
Sex differences in (+)-amphetamine- and (+)-methamphetamine-induced behavioral response in male and female Sprague-Dawley rats
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DOI：
10.1016/j.pbb.2006.12.018
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发表时间：
2007-01-01
影响因子：
3.6
通讯作者：
Owens, S. Michael
中科院分区：
文献类型：
--
作者：
Milesi-Halle, Alessandra;McMillan, Donald E.;Owens, S. Michael
（+）-甲基苯丙胺（METH）和（+）-苯丙胺（AMP）是结构相似的药物，据报告在相同性别的大鼠中诱导相似的药理学作用。由于药代动力学数据表明雌性大鼠应比雄性大鼠受影响更大，因此目前的研究试图检验METH和AMP在雌性Sprague-Dawley大鼠中的行为和时间作用应大于雄性大鼠的假设。采用旨在降低耐受性和致敏性可能性的给药方案，对大鼠静脉给予1.0和3.0 mg/kg药物剂量。移动的距离，饲养事件和焦点刻板印象（例如，头摆动、嗅闻）。雌性大鼠旅行的距离显着更大，并显示了更多的饲养事件比雄性后，两个剂量。3.0 mg/kg剂量给药后的刻板印象评级分析显示，雌性动物的局灶性刻板印象更明显，持续时间更长。第二项研究比较了METH和AMP在诱导每种性别的自发活动和局灶性刻板印象方面的效力。在雄性或雌性动物中比较METH和AMP效应时，未发现效力差异。总之，这些研究表明雌性大鼠表现出更大和更持久的运动活动和更多的刻板行为，支持药代动力学显著性二态性的早期证据。(c)2007 Osevier Inc. All rights reserved.
(+)-Methamphetamine (METH) and (+)-amphetamine (AMP) are structurally similar drugs that are reported to induce similar pharmacological effects in rats of the same sex. Because pharmacokinetic data suggest female rats should be more affected than males, the current studies sought to test the hypothesis that the behavioral and temporal actions of METH and AMP should be greater in female Sprague-Dawley rats than in males. Using a dosing regimen designed to reduce the possibility of tolerance and sensitization, rats were administered 1.0 and 3.0 mg/kg intravenous drug doses. Distance traveled, rearing events and focal stereotypies (e.g., head weaving, sniffing) were measured. Female rats traveled significantly greater distances and displayed a greater number of rearing events than males after both doses. Analysis of stereotypy ratings after 3.0 mg/kg revealed that focal stereotypies were more pronounced and lasted longer in females. The second study compared the potencies of METH and AMP in inducing locomotor activity and focal stereotypies in each sex. No differences in potency were found when METH and AMP effects were compared within males or females. In summary, these studies showed female rats displayed greater and longer-lasting locomotor activity and more stereotypic behaviors, supporting earlier evidence of significant sexual dimorphism in pharmacokinetics. (c) 2007 Osevier Inc. All rights reserved.