Effects of monoamine oxidase inhibitors on cocaine discrimination in rats.
Effects of monoamine oxidase inhibitors on cocaine discrimination in rats.
复制标题
单胺氧化酶抑制剂对大鼠可卡因辨别的影响。
DOI：
10.1097/01.fbp.0000197459.08892.b5
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发表时间：
2006
影响因子：
1.6
通讯作者：
Forster,MichaelJ
中科院分区：
文献类型：
--
作者：
Gatch,MichaelB;Taylor,CynthiaM;Flores,Elva;Selvig,Meghan;Forster,MichaelJ
本研究测试了单胺氧化酶抑制剂单独或与可卡因组合的辨别刺激效应的时间过程。训练雄性Sprague-Dawley大鼠使用双杠杆选择方法区分可卡因（10 mg/kg，腹膜内）和盐水。非选择性单胺氧化酶抑制剂反苯环丙胺（0.01-5 mg/kg）和苯乙肼（1-25 mg/kg），单胺氧化酶-A选择性化合物氯吉林（1-25 mg/kg），以及单胺氧化酶-B选择性化合物帕吉林（0.005-50 mg/kg）和司来吉兰在给药后15分钟或24小时，以及在给药后24和48小时与10 mg/kg可卡因组合，测试了（1-25 mg/kg）的替代。在15分钟时，司来吉兰完全取代可卡因的辨别刺激作用，而所有其他化合物部分取代。在24小时，可卡因的替代减少了所有化合物，除了苯乙肼，产生了更大的量在24小时比在15分钟的替代。当可卡因给药后24小时，氯吉兰，司来吉兰，帕吉林，苯乙肼，可卡因适当的响应衰减在这些药物的中间剂量，而最高剂量并没有改变可卡因杠杆反应。除司来吉兰外，所有化合物均显著降低应答率，并产生各种不良反应。在48 h时，除苯乙肼外，所有化合物的作用均显著降低。单胺氧化酶-A或单胺氧化酶-B的选择性并不能预测替代或减弱可卡因主观效应的能力。这些结果表明，单胺氧化酶抑制剂可以调节可卡因的歧视性刺激效应至少24小时，并可能是有用的可卡因滥用的治疗。
This study tested the time course of the discriminative stimulus effects of inhibitors of monoamine oxidase alone or in combination with cocaine. Male Sprague–Dawley rats were trained to discriminate cocaine (10 mg/kg, intraperitoneal) from saline using a two-lever choice methodology. The nonselective monoamine oxidase inhibitors tranylcypromine (0.01–5 mg/kg) and phenelzine (1–25 mg/kg), the monoamine oxidase-A selective compound clorgyline (1–25 mg/kg), and the monoamine oxidase-B selective compounds pargyline (0.005–50 mg/kg) and selegiline (1–25 mg/kg) were tested for substitution 15 min or 24 h following administration, and in combination with 10 mg/kg of cocaine 24 and 48 h after administration. At 15 min, selegiline fully substituted for the discriminative stimulus effects of cocaine, whereas all other compounds partially substituted. At 24 h, substitution of cocaine was diminished for all compounds except phenelzine, which produced a greater amount of substitution at 24 h than at 15 min. When cocaine was administered 24 h after clorgyline, selegiline, pargyline, and phenelzine, cocaine-appropriate responding was attenuated at intermediate doses of these drugs, whereas the highest doses did not alter cocaine-lever responding. All compounds except selegiline substantially decreased response rate and produced various adverse effects. At 48 h, the effects of all compounds except phenelzine were markedly reduced. Selectivity for monoamine oxidase-A or monoamine oxidase-B did not predict the ability to substitute for or attenuate the subjective effects of cocaine. These findings suggest that monoamine oxidase inhibitors can modulate the discriminative stimulus effects of cocaine for at least 24 h, and may be useful for treatment of cocaine abuse.