Adell Albert, Celada Pau, Abellán M Teresa, Artigas Francesc
Department of Neurochemistry, Institut d'Investigacions Biomèdiques de Barcelona, CSIC (IDIBAPS), Carrer Rosselló 161, 6th floor, E-08036 Barcelona, Spain.
Brain Res Brain Res Rev. 2002 Sep;39(2-3):154-80. doi: 10.1016/s0165-0173(02)00182-0.
There is considerable interest in the regulation of the extracellular compartment of the transmitter serotonin (5-hydroxytryptamine, 5-HT) in the midbrain raphe nuclei because it can control the activity of ascending serotonergic systems and the release of 5-HT in terminal areas of the forebrain. Several intrinsic and extrinsic factors of 5-HT neurons that regulate 5-HT release in the dorsal (DR) and median (MnR) raphe nucleus are reviewed in this article. Despite its high concentration in the extracellular space of the raphe nuclei, the origin of this pool of the transmitter remains to be determined. Regardless of its origin, is has been shown that the release of 5-HT in the rostral raphe nuclei is partly dependent on impulse flow and Ca(2+) ions. The release in the DR and MnR is critically dependent on the activation of 5-HT autoreceptors in these nuclei. Yet, it appears that 5-HT autoreceptors do not tonically inhibit 5-HT release in the raphe nuclei but rather play a role as sensors that respond to an excess of the endogenous transmitter. Both DR and MnR are equally responsive to the reduction of 5-HT release elicited by the local perfusion of 5-HT(1A) receptor agonists. In contrast, the effects of selective 5-HT(1B) receptor agonists are more pronounced in the MnR than in the DR. However, the cellular localization of 5-HT(1B) receptors in the raphe nuclei remains to be established. Furthermore, endogenous noradrenaline and GABA tonically regulate the extracellular concentration of 5-HT although the degree of tonicity appears to depend upon the sleep/wake cycle and the behavioral state of the animal. Glutamate exerts a phasic facilitatory control over the release of 5-HT in the raphe nuclei through ionotropic glutamate receptors. Overall, it appears that the extracellular concentration of 5-HT in the DR and the MnR is tightly controlled by intrinsic serotonergic mechanisms as well as afferent connections.
中脑缝核中递质5-羟色胺（5-羟色胺，5-HT）细胞外区室的调节备受关注，因为它可以控制上行5-羟色胺能系统的活性以及前脑终末区域5-HT的释放。本文综述了调节背侧（DR）和中缝（MnR）缝核中5-HT释放的5-HT神经元的几种内在和外在因素。尽管其在缝核细胞外空间中浓度很高，但该递质池的来源仍有待确定。无论其来源如何，已经表明，在吻侧缝核中5-HT的释放部分依赖于冲动流和Ca(2+)离子。DR和MnR中的释放关键取决于这些核中5-HT自身受体的激活。然而，5-HT自身受体似乎并非持续性地抑制缝核中5-HT的释放，而是作为对内源性递质过量做出反应的传感器发挥作用。DR和MnR对5-HT(1A)受体激动剂局部灌注引起的5-HT释放减少具有同等反应性。相比之下，选择性5-HT(1B)受体激动剂在MnR中的作用比在DR中更明显。然而，5-HT(1B)受体在缝核中的细胞定位仍有待确定。此外，内源性去甲肾上腺素和GABA持续性地调节5-HT的细胞外浓度，尽管其紧张性程度似乎取决于睡眠/觉醒周期和动物的行为状态。谷氨酸通过离子型谷氨酸受体对缝核中5-HT的释放施加阶段性促进控制。总体而言，DR和MnR中5-HT的细胞外浓度似乎受到内在5-羟色胺能机制以及传入连接的严格控制。
