Schad C A, Justice J B, Holtzman S G
Department of Pharmacology, Emory University, Atlanta, GA 30322, USA.
Eur J Pharmacol. 1995 Feb 24;275(1):9-16. doi: 10.1016/0014-2999(94)00726-n.
The specific opioid receptor antagonist naloxone modifies the effects of amphetamine in a wide variety of behavioral paradigms. Naloxone also attenuates the amphetamine-induced increase in extracellular dopamine in the brain of rats. Therefore, these experiments were designed to replicate the neurochemical and behavioral interactions between naloxone and amphetamine, and to extend these observations to interactions between naloxone and cocaine. Microdialysis was performed on adult male rats of Sprague-Dawley descent. Rats were pretreated with a subcutaneous injection of 5.0 mg/kg naloxone or vehicle, which was followed 30 min later by cumulative doses of subcutaneous d-amphetamine (0.0, 0.1, 0.4, 1.6, 6.4 mg/kg) or intraperitoneal cocaine (0, 3, 10, 30, 56 mg/kg) at 30 min intervals. The microdialysis probes were perfused at a flow rate of 0.6 microliter/min with artificial cerebrospinal fluid. Dialysate samples were collected every 10 min from either the nucleus accumbens or striatum and analyzed for dopamine content by high-performance liquid chromatography (HPLC). Locomotor activity (photobeam breaks) was monitored simultaneously with the collection of dialysate samples. Amphetamine and cocaine dose-dependently increased extracellular dopamine in both the nucleus accumbens and striatum. Naloxone pretreatment significantly reduced the amphetamine-induced increase in extracellular dopamine in both brain regions and also attenuated the increase in locomotor activity elicited by amphetamine. Naloxone pretreatment had no effect, however, on the cocaine-induced increase in extracellular dopamine or locomotor activity. These findings suggest that endogenous opioid systems play a role in mediating the neurochemical and behavioral effects of amphetamine, but not those of cocaine.
特异性阿片受体拮抗剂纳洛酮可在多种行为范式中改变苯丙胺的作用。纳洛酮还可减弱苯丙胺引起的大鼠脑内细胞外多巴胺水平升高。因此，设计这些实验旨在重现纳洛酮与苯丙胺之间的神经化学和行为相互作用，并将这些观察结果扩展至纳洛酮与可卡因之间的相互作用。对成年雄性斯普拉格 - 道利品系大鼠进行微透析。大鼠皮下注射5.0mg/kg纳洛酮或赋形剂进行预处理，30分钟后，每隔30分钟皮下注射累积剂量的d - 苯丙胺（0.0、0.1、0.4、1.6、6.4mg/kg）或腹腔注射可卡因（0、3、10、30、56mg/kg）。微透析探针以0.6微升/分钟的流速用人工脑脊液灌注。每隔10分钟从伏隔核或纹状体收集透析液样本，并通过高效液相色谱法（HPLC）分析多巴胺含量。在收集透析液样本的同时监测运动活性（光束中断）。苯丙胺和可卡因均剂量依赖性地增加伏隔核和纹状体内的细胞外多巴胺水平。纳洛酮预处理显著降低了两个脑区中苯丙胺诱导的细胞外多巴胺水平升高，也减弱了苯丙胺引起的运动活性增加。然而，纳洛酮预处理对可卡因诱导的细胞外多巴胺水平升高或运动活性没有影响。这些发现表明，内源性阿片系统在介导苯丙胺的神经化学和行为效应中起作用，但在介导可卡因的这些效应中不起作用。
