INFLUENCE OF TETRODOTOXIN AND CALCIUM ON CHANGES IN EXTRACELLULAR DOPAMINE LEVELS EVOKED BY SYSTEMIC NICOTINE
INFLUENCE OF TETRODOTOXIN AND CALCIUM ON CHANGES IN EXTRACELLULAR DOPAMINE LEVELS EVOKED BY SYSTEMIC NICOTINE
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DOI：
10.1007/bf02244896
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发表时间：
1993-10-01
影响因子：
3.4
通讯作者：
LUCCHI, HM
中科院分区：
文献类型：
--
作者：
BENWELL, MEM;BALFOUR, DJK;LUCCHI, HM
在清醒、自由活动的大鼠中，应用体内微透析技术，研究了河豚毒素（TTX）和钙离子对全身给予尼古丁、可卡因和d-苯丙胺引起的丘脑核（NAcc）细胞外多巴胺（DA）水平增加的影响。经透析探头给予TTX（10（-6）M）可完全消除（P < 0.01）尼古丁（0.4 mg/kg SC）给药后细胞外DA、DOPAC和HVA的升高。在林格氏液中加入乙二胺四乙酸（EDTA 10（-4）M）以除去钙，也与抑制尼古丁引起的这些参数的变化有关（P < 0.01）。可卡因（15 mg/kg IP）和d-苯丙胺（0.5 mg/kg SC）的全身给药引起细胞外DA升高（P < 0.01），同时HVA水平显著降低（P < 0.01）。D-苯丙胺治疗也显著降低DOPAC水平（P < 0.01）。TTX的存在和钙的去除与添加EDTA完全取消了可卡因引起的NAcc DA和HVA的变化。TTX对D-苯丙胺诱发的NAcc DA反应没有影响。然而，被TTX显著减少的代谢物，并没有被D-苯丙胺的全身给药进一步减少。在无钙和有EDTA的情况下，D-苯丙胺使NAcc DA显著升高（P < 0.01）。然而，与在钙存在下观察到的相比，这显著（P < 0.01）减弱。结果支持以下结论：在测试剂量下，尼古丁通过钙和脉冲依赖性机制引起细胞外NAcc DA水平增加。此外，这些数据也是一致的部分钙依赖性的组件在体内的d-苯丙胺诱导的刺激该系统。
The influence of tetrodotoxin (TTX) and calcium on the increase of extracellular dopamine (DA) levels in the nucleus accumbens (NAcc), evoked by the systemic administration of nicotine, cocaine and d-amphetamine, have been studied in conscious, freely moving rats using in vivo microdialysis. TTX (10(-6) M), administered via the dialysis probe, completely abolished (P < 0.01) the elevations in extracellular DA, DOPAC and HVA seen following nicotine (0.4 mg/kg SC). The removal of calcium with the inclusion of diaminoethanete-traacetic acid (EDTA 10(-4) M) in the Ringer solution was also associated with inhibition (P < 0.01) of the nicotine-induced changes in these parameters. The systemic administration of cocaine (15 mg/kg IP) and d-amphetamine (0.5 mg/kg SC) caused elevations in extracellular DA (P < 0.01) accompanied by significant decreases (P < 0.01) in HVA levels. DOPAC levels were also significantly (P < 0.01) lowered by d-amphetamine treatment. The presence of TTX and removal of calcium with addition of EDTA completely abolished the changes in NAcc DA and HVA induced by cocaine. TTX had no influence on the d-amphetamine evoked responses in NAcc DA. However, the metabolites, which were markedly reduced by the TTX, were not further decreased by the systemic administration of d-amphetamine. NAcc DA was significantly (P < 0.01) raised following d-amphetamine in the absence of calcium and presence of EDTA. However, this was significantly (P < 0.01) attenuated in comparison to that seen in the presence of calcium. The results support the conclusion that, at the dose tested, nicotine evokes increases in extracellular NAcc DA levels by calcium and impulse-dependent mechanisms. Moreover, the data are also consistent with a partial calcium-dependent component in d-amphetamine-induced stimulation of this system in vivo.