The effect of methamphetamine on an animal model of erectile function.
The effect of methamphetamine on an animal model of erectile function.
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甲基苯丙胺对勃起功能动物模型的影响。
DOI：
10.1111/j.2047-2927.2014.00212.x
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发表时间：
2014
期刊：
影响因子：
4.5
通讯作者：
Davies,KP
中科院分区：
文献类型：
--
作者：
Tar,MT;Martinez,LR;Nosanchuk,JD;Davies,KP
在美国，甲基苯丙胺被认为是治疗注意缺陷多动障碍的一线药物。它也是一种常见的滥用药物。患者和滥用者的报告表明其使用导致阳痿。磷酸二酯酶-5抑制剂（PDE 5i）在这些患者组中恢复勃起功能的疗效也尚未确定。在这些研究中，我们确定了大鼠是否是甲基苯丙胺对勃起功能的生理作用的合适动物模型，以及PDE 5i（他达拉非）是否对甲基苯丙胺治疗后的勃起功能有影响。在急性期研究中，在10 mg/kg甲基苯丙胺i. p.给药前后，测量雄性Sprague-道利大鼠的勃起功能。长期给药动物接受递增剂量的甲基苯丙胺[2.5 mg/kg（第1周）、5 mg/kg（第2周）和10 mg/kg（第3周）] i. p.每日一次，持续3周，并与未给药对照组比较勃起功能。还在甲基苯丙胺急性和慢性给药大鼠中研究了他达拉非联合给药的影响。勃起功能通过测量海绵体神经刺激后的颅内压/血压比（ICP/BP）来确定。在急性期和慢性期研究中，我们观察到甲基苯丙胺给药后自发勃起率显著增加。此外，在4和6 mA刺激海绵体神经后，ICP/BP比值显著降低（约50%），表明勃起功能受损。他达拉非治疗逆转了这一效应。在长期给药动物中，与未给药动物相比，4 mA和6 mA刺激后的ICP/BP比值降低约50%，他达拉非也逆转了勃起功能障碍（艾德）。总的来说，我们的数据表明，大鼠是一个合适的动物模型，以研究甲基苯丙胺对勃起功能的生理作用。我们的工作还为治疗报告与含甲基苯丙胺或苯丙胺的治疗药物（PDE 5 i）相关的艾德患者提供了依据。
In the US methamphetamine is considered a first‐line treatment for attention‐deficit hyperactivity disorder. It is also a common drug of abuse. Reports in patients and abusers suggest its use results in impotence. The efficacy of phosphodiesterase‐5 inhibitors (PDE5i) to restore erectile function in these patient groups also has not been determined. In these studies, we determined if the rat is a suitable animal model for the physiological effects of methamphetamine on erectile function, and if a PDE5i (tadalafil) has an effect on erectile function following methamphetamine treatment. In acute phase studies, erectile function was measured in male Sprague‐Dawley rats, before and after administration of 10 mg/kg methamphetamine i.p. Chronically treated animals received escalating doses of methamphetamine [2.5 mg/kg (1st week), 5 mg/kg (2nd week), and 10 mg/kg (3rd week)] i.p. daily for 3 weeks and erectile function compared with untreated controls. The effect of co‐administration of tadalafil was also investigated in rats acutely and chronically treated with methamphetamine. Erectile function was determined by measuring the intracorporal pressure/blood pressure ratio (ICP/BP) following cavernous nerve stimulation. In both acute and chronic phase studies, we observed a significant increase in the rates of spontaneous erections after methamphetamine administration. In addition, following stimulation of the cavernous nerve at 4 and 6 mA, there was a significant decrease in the ICP/BP ratio (approximately 50%), indicative of impaired erectile function. Tadalafil treatment reversed this effect. In chronically treated animals, the ICP/BP ratio following 4 and 6 mA stimulation decreased by approximately 50% compared with untreated animals and erectile dysfunction (ED) was also reversed by tadalafil. Overall, our data suggest that the rat is a suitable animal model to study the physiological effect of methamphetamine on erectile function. Our work also provides a rationale for treating patients that report ED associated with therapeutics‐containing methamphetamine or amphetamine with PDE5i.