Amphetamine maintenance is effective clinically to reduce the consumption of the monoamine uptake inhibitor cocaine but not of the monoamine releaser methamphetamine, and its effectiveness in treating the abuse of other psychostimulants is not known. The mechanisms for differential amphetamine-maintenance effectiveness to treat different types of psychostimulant abuse are also not known. Accordingly, the present study compared the effects of amphetamine maintenance on abuse-related behavioral and neurochemical effects of cocaine, methamphetamine, and the "bath salts" constituent 3,4-methylenedioxypyrovalerone (MDPV) in rats. In behavioral studies, rats were trained to lever press for electrical brain stimulation in an intracranial self-stimulation (ICSS) procedure. In neurochemical studies, nucleus accumbens (NAc) levels of dopamine (DA) and serotonin (5-HT) were monitored by in vivo microdialysis. Cocaine, methamphetamine, and MDPV each produced dose-dependent ICSS facilitation and increases in NAc DA; cocaine and methamphetamine also increased NAc 5-HT. Amphetamine maintenance (0.32 mg/kg/h × 7 days) produced (1) sustained increases in basal ICSS and NAc DA with no change in NAc 5-HT, (2) blockade of cocaine but not methamphetamine effects on ICSS and NAc DA, and (3) no blockade of cocaine- or methamphetamine-induced increases in NAc 5-HT. Amphetamine maintenance blocked the increases in NAc DA produced by the selective DA uptake inhibitor MDPV, but it did not block MDPV-induced ICSS facilitation. These results show different effects of amphetamine maintenance on behavioral and neurochemical effects of different psychostimulants. The selective effectiveness of amphetamine maintenance to treat cocaine abuse may reflect attenuation of cocaine-induced increases in NAc DA while preserving cocaine-induced increases in NAc 5-HT.

中文翻译：

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苯丙胺维持剂差异性地调节可卡因，亚甲基二氧基吡咯烷酮（MDPV）和甲基苯丙胺对大鼠颅内自我刺激和伏隔核多巴胺的作用。

苯丙胺维护在临床上可有效减少单胺摄取抑制剂可卡因的消耗，但不能减少单胺释放剂甲基苯丙胺的消耗，其在治疗其他精神兴奋剂滥用中的有效性尚不明确。还不清楚用于维持不同类型精神兴奋剂滥用的维持苯丙胺的有效性差异的机制。因此，本研究比较了苯丙胺维持对可卡因，甲基苯丙胺和“沐浴盐”成分3,4-亚甲基二氧基吡咯烷酮（MDPV）中与滥用相关的行为和神经化学作用的影响。在行为研究中，对大鼠进行了颅内自我刺激（ICSS）程序中的杠杆压迫训练，以进行电脑刺激。在神经化学研究中 通过体内微透析监测伏隔核（NAc）多巴胺（DA）和5-羟色胺（5-HT）的水平。可卡因，甲基苯丙胺和MDPV均可产生剂量依赖性的ICSS促进作用，并增加NAc DA。可卡因和甲基苯丙胺也增加了NAc 5-HT。产生的苯丙胺维持量（0.32 mg / kg / h×7天）（1）基础ICSS和NAc DA持续增加，而NAc 5-HT无变化；（2）阻断可卡因，但对ICSS和NAc DA的甲基苯丙胺没有影响， （3）没有阻止可卡因或甲基苯丙胺引起的NAc 5-HT升高。苯丙胺的维持阻止了选择性DA摄取抑制剂MDPV产生的NAc DA的增加，但并未阻止MDPV诱导的ICSS促进作用。这些结果表明苯丙胺维持对不同精神刺激药的行为和神经化学作用的不同影响。