Morgan A E, Porter S P, Clarkson F A, Volkow N D, Fowler J S, Dewey S L
Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973, USA.
Synapse. 1997 Aug;26(4):423-7. doi: 10.1002/(SICI)1098-2396(199708)26:4<423::AID-SYN10>3.0.CO;2-U.
Using in vivo microdialysis techniques, the effects of RTI-55 and/or cocaine on extracellular dopamine (DA) concentrations were measured in the nucleus accumbens (NACC) of freely moving rats. In control animals, cocaine (20 mg/kg) increased NACC DA approximately 458% 60 minutes following administration, returning to baseline values within 200 minutes. Similarly, RTI-55 administration (0.25 mg/kg) increased NACC DA levels approximately 347%. When combined, however, cocaine further increased NACC DA to 705% of baseline values when given 4 hours following RTI-55. This increase was significantly larger than cocaine alone (P < 0.05). In addition, chronic RTI-55 administration (5 days) further potentiated cocaine's ability to increase NACC DA (783%) but this did not reach statistical significance (P > 0.1) compared to acute RTI55/cocaine animals. These findings indicate that RTI-55, a drug that binds directly to the dopamine transporter (DAT) with higher affinity than cocaine, does not appear to be effective in attenuating cocaine's effects on NACC dopamine levels. In fact, acute RTI-55 potentiates cocaine's effects on NACC DA.
运用体内微透析技术，在自由活动大鼠的伏隔核（NACC）中测量了RTI - 55和/或可卡因对细胞外多巴胺（DA）浓度的影响。在对照动物中，可卡因（20毫克/千克）给药后60分钟，伏隔核多巴胺增加约458%，并在200分钟内恢复至基线值。同样，给予RTI - 55（0.25毫克/千克）可使伏隔核多巴胺水平增加约347%。然而，联合使用时，在给予RTI - 55 4小时后再给予可卡因，伏隔核多巴胺进一步增加至基线值的705%。这种增加显著大于单独使用可卡因时（P < 0.05）。此外，长期给予RTI - 55（5天）进一步增强了可卡因增加伏隔核多巴胺的能力（783%），但与急性给予RTI - 55/可卡因的动物相比，这未达到统计学显著性（P > 0.1）。这些发现表明，RTI - 55这种比可卡因以更高亲和力直接结合多巴胺转运体（DAT）的药物，似乎在减弱可卡因对伏隔核多巴胺水平的影响方面无效。事实上，急性给予RTI - 55会增强可卡因对伏隔核多巴胺的作用。
