Gresch P J, Sved A F, Zigmond M J, Finlay J M
Department of Neuroscience, University of Pittsburgh, Pennsylvania 15260, USA.
J Neurochem. 1995 Jul;65(1):111-6. doi: 10.1046/j.1471-4159.1995.65010111.x.
Noradrenergic and dopaminergic projections converge in the medial prefrontal cortex and there is evidence of an interaction between dopamine (DA) and norepinephrine (NE) terminals in this region. We have examined the influence of drugs known to alter extracellular NE on extracellular NE and DA in medial prefrontal cortex using in vivo microdialysis. Local application of the NE uptake inhibitor desipramine (1.0 microM) delivered through a microdialysis probe increased extracellular DA (+149%) as well as NE (+201%) in medial prefrontal cortex. Furthermore, desipramine potentiated the tail shock-induced increase in both extracellular DA (stress alone, +64%; stress + desipramine, +584%) and NE (stress alone, +55%; stress + desipramine, +443%). In contrast, local application of desipramine did not affect extracellular DA in striatum, indicating that this drug does not influence DA efflux directly. Local application of the alpha 2-adrenoceptor antagonist idazoxan (0.1 or 5.0 mM) increased extracellular NE and DA in medial prefrontal cortex. Conversely, the alpha 2-adrenoceptor agonist clonidine (0.2 mg/kg; i.p.) decreased extracellular NE and DA in medial prefrontal cortex. These results support the hypothesis that NE terminals in medial prefrontal cortex regulate extracellular DA in this region. This regulation may be achieved by mechanisms involving an action of NE on receptors that regulate DA release (heteroreceptor regulation) and/or transport of DA into noradrenergic terminals (heterotransporter regulation).
去甲肾上腺素能和多巴胺能投射在内侧前额叶皮质汇聚，并且有证据表明该区域多巴胺（DA）和去甲肾上腺素（NE）终末之间存在相互作用。我们使用体内微透析技术，研究了已知可改变细胞外NE的药物对内侧前额叶皮质细胞外NE和DA的影响。通过微透析探针局部应用NE摄取抑制剂地昔帕明（1.0微摩尔），可使内侧前额叶皮质细胞外DA增加（+149%）以及NE增加（+201%）。此外，地昔帕明增强了尾部电击诱导的细胞外DA（单独应激时增加+64%；应激+地昔帕明时增加+584%）和NE（单独应激时增加+55%；应激+地昔帕明时增加+443%）的升高。相比之下，局部应用地昔帕明对纹状体细胞外DA没有影响，表明该药物不直接影响DA流出。局部应用α2-肾上腺素能受体拮抗剂咪唑克生（0.1或5.0毫摩尔）可增加内侧前额叶皮质细胞外NE和DA。相反，α2-肾上腺素能受体激动剂可乐定（0.2毫克/千克；腹腔注射）可降低内侧前额叶皮质细胞外NE和DA。这些结果支持内侧前额叶皮质中的NE终末调节该区域细胞外DA的假说。这种调节可能通过涉及NE作用于调节DA释放的受体（异受体调节）和/或将DA转运到去甲肾上腺素能终末（异转运体调节）的机制来实现。
