Schad C A, Justice J B, Holtzman S G
Department of Pharmacology, Emory University, Atlanta, Georgia 30322, USA.
J Neurochem. 1996 Dec;67(6):2292-9. doi: 10.1046/j.1471-4159.1996.67062292.x.
The specific opioid receptor antagonist naloxone attenuates the behavioral and neurochemical effects of amphetamine. Furthermore, the amphetamine-induced increase in locomotor activity is attenuated by intracisternally administered naltrindole, a selective delta-opioid receptor antagonist, but not by the irreversible mu-opioid receptor antagonist beta-funaltrexamine. Therefore, this research was designed to determine if naltrindole would attenuate the neurochemical response to amphetamine as it did the behavioral response. In vivo microdialysis was used to monitor the change in extracellular concentrations of dopamine in awake rats. Naltrindole (3.0, 10, or 30 micrograms) or vehicle was given 15 min before and beta-funaltrexamine (10 micrograms) or vehicle 24 h before the start of cumulative dosing, intracisternally in a 10-microliters volume, while the rats were lightly anesthetized with methoxyflurane. Cumulative doses of subcutaneous d-amphetamine (0.0, 0.1, 0.4, 1.6, and 6.4 mg/kg) followed pretreatment injections at 30-min intervals. Dialysate samples were collected every 10 min from either the striatum or nucleus accumbens and analyzed for dopamine content by HPLC. Amphetamine dose-dependently increased dopamine content in both the striatum and nucleus accumbens, as reported previously. Naltrindole (3.0, 10, and 30 micrograms) significantly reduced the dopamine response to amphetamine in the striatum. In contrast, 30 micrograms of naltrindole did not modify the dopamine response to amphetamine in the nucleus accumbens. On the other hand, beta-funaltrexamine (10 micrograms) had no effect in the striatum but significantly attenuated the amphetamine-induced increase in extracellular dopamine content in the nucleus accumbens. These data suggest that delta-opioid receptors play a relatively larger role than mu-opioid receptors in mediating the amphetamine-induced increase in extracellular dopamine content in the striatum, whereas mu-opioid receptors play a larger role in mediating these effects in the nucleus accumbens.
特异性阿片受体拮抗剂纳洛酮可减弱苯丙胺的行为和神经化学效应。此外，脑池内注射选择性δ-阿片受体拮抗剂纳曲吲哚可减弱苯丙胺引起的运动活动增加，但不可逆的μ-阿片受体拮抗剂β-氟纳曲明则无此作用。因此，本研究旨在确定纳曲吲哚是否会像减弱行为反应一样减弱对苯丙胺的神经化学反应。采用体内微透析技术监测清醒大鼠细胞外多巴胺浓度的变化。在累积给药开始前15分钟，脑池内注射纳曲吲哚（3.0、10或30微克）或溶剂，在开始累积给药前24小时，脑池内注射β-氟纳曲明（10微克）或溶剂，体积为10微升，同时用甲氧氟烷对大鼠进行轻度麻醉。皮下注射d-苯丙胺（0.0、0.1、0.4、1.6和6.4毫克/千克）的累积剂量，每隔30分钟进行一次预处理注射。每隔10分钟从纹状体或伏隔核收集透析液样本，并通过高效液相色谱法分析多巴胺含量。如先前报道，苯丙胺剂量依赖性地增加了纹状体和伏隔核中的多巴胺含量。纳曲吲哚（3.0、10和30微克）显著降低了纹状体中多巴胺对苯丙胺的反应。相比之下，30微克纳曲吲哚并未改变伏隔核中多巴胺对苯丙胺的反应。另一方面，β-氟纳曲明（10微克）对纹状体无影响，但显著减弱了苯丙胺引起的伏隔核细胞外多巴胺含量增加。这些数据表明，在介导苯丙胺引起的纹状体细胞外多巴胺含量增加方面，δ-阿片受体比μ-阿片受体发挥的作用相对更大，而在介导伏隔核中的这些效应方面，μ-阿片受体发挥的作用更大。
