Fulford A J, Marsden C A
Department of Anatomy, University of Bristol, Southwell Street, Bristol BS2 8EJ, UK.
Neuroscience. 2007 Oct 26;149(2):392-400. doi: 10.1016/j.neuroscience.2007.08.002. Epub 2007 Aug 8.
We investigated the effect of the tyrosine hydroxylase inhibitor, alpha-methyl-para-tyrosine (AMPT) on extracellular dopamine and 5-HT levels in the nucleus accumbens of group- and isolation-reared rats. Microdialysis with high-performance liquid chromatography-electrochemical detection was used to quantify dopamine and 5-HT efflux in the nucleus accumbens following foot shock and in association with a conditioned emotional response (CER). Isolation- and group-reared rats received i.p. injections of either saline (0.9%) or AMPT (200 mg/kg) 15 h and 2 h prior to sampling. There was no significant difference between saline-treated isolation- or group-reared rats for basal efflux of dopamine or 5-HT, however as expected, AMPT-treatment significantly reduced dopamine efflux in both groups to an equivalent level (50-55% saline-treated controls). Exposure to mild foot shock stimulated basal dopamine efflux in saline-treated groups only, although the effect was significantly greater in isolation-reared rats. In AMPT-treated rats, foot shock did not affect basal dopamine efflux in either rearing group. Foot shock evoked a prolonged increase in 5-HT efflux in both isolation- and group-reared saline-treated rats but had no effect on 5-HT efflux in AMPT-treated rats. In response to CER, isolation-rearing was associated with significantly greater efflux of both dopamine and 5-HT in saline-treated rats, compared to saline-treated, group-reared controls. However in AMPT-treated rats, efflux of dopamine or 5-HT did not change in response to CER. These data suggest that unconditioned or conditioned stress-induced changes in 5-HT release of the nucleus accumbens are dependent upon intact catecholaminergic neurotransmission. Furthermore, as the contribution of noradrenaline to catecholamine efflux in the nucleus accumbens is relatively minor compared to dopamine, our findings suggest that dopamine efflux in the nucleus accumbens is important for the local regulation of 5-HT release in this region. Finally, these findings implicate the isolation-enhanced presynaptic dopamine function in the accumbens with the augmented ventral striatal 5-HT neurotransmission characterized by isolation-reared rats.
我们研究了酪氨酸羟化酶抑制剂α-甲基-对酪氨酸（AMPT）对群居和隔离饲养大鼠伏隔核细胞外多巴胺和5-羟色胺（5-HT）水平的影响。采用高效液相色谱-电化学检测微透析技术，对足部电击后以及与条件性情绪反应（CER）相关的伏隔核中多巴胺和5-HT的流出量进行定量分析。隔离饲养和群居饲养的大鼠在取样前15小时和2小时腹腔注射生理盐水（0.9%）或AMPT（200mg/kg）。生理盐水处理的隔离饲养或群居饲养大鼠的多巴胺或5-HT基础流出量之间没有显著差异，然而，正如预期的那样，AMPT处理显著降低了两组中的多巴胺流出量至同等水平（生理盐水处理对照组的50-55%）。仅在生理盐水处理组中，暴露于轻度足部电击刺激了基础多巴胺流出量，尽管在隔离饲养大鼠中的作用明显更大。在AMPT处理的大鼠中，足部电击对任一饲养组的基础多巴胺流出量均无影响。足部电击在隔离饲养和群居饲养的生理盐水处理大鼠中均引起5-HT流出量的长时间增加，但对AMPT处理的大鼠的5-HT流出量没有影响。对于CER，与生理盐水处理的群居饲养对照相比，隔离饲养与生理盐水处理大鼠中多巴胺和5-HT的流出量显著增加有关。然而，在AMPT处理的大鼠中，多巴胺或5-HT的流出量对CER没有变化。这些数据表明，伏隔核中5-HT释放的无条件或条件性应激诱导变化依赖于完整的儿茶酚胺能神经传递。此外，由于与多巴胺相比，去甲肾上腺素对伏隔核中儿茶酚胺流出量的贡献相对较小，我们的研究结果表明伏隔核中的多巴胺流出量对于该区域5-HT释放的局部调节很重要。最后，这些研究结果表明，隔离增强的伏隔核突触前多巴胺功能与隔离饲养大鼠所特有的腹侧纹状体5-HT神经传递增强有关。
