Engin E, Stellbrink J, Treit D, Dickson C T
Department of Psychology, University of Alberta, P-449 Biological Sciences Building, Edmonton, AB, Canada T6G 2E9.
Neuroscience. 2008 Dec 2;157(3):666-76. doi: 10.1016/j.neuroscience.2008.09.037. Epub 2008 Oct 2.
Somatostatin (SST) is a cyclic polypeptide that inhibits the release of a variety of regulatory hormones (e.g. growth hormone, insulin, glucagon, thyrotropin). Moreover, SST is widely distributed within the CNS, acting both as a neurotransmitter and as a neuromodulator of other neurotransmitter systems. However, despite its extensive expression in limbic areas, and its co-localization with GABA, a neurotransmitter previously implicated in emotion, the effects of SST on anxiety and depression have not been investigated. By performing intraventricular infusions in rats we demonstrate, for the first time, that SST has anxiolytic- and antidepressant-like effects in the elevated plus-maze and forced swim test, respectively. In addition, by performing local field potential recordings of hippocampal theta activity evoked by reticular stimulation in urethane-anesthetized rats we also show that SST application suppresses the frequency of theta in a similar fashion to diazepam. This neurophysiological signature, common to all classes of anxiolytic drugs (i.e. benzodiazepines, selective 5-HT reuptake inhibitors, 5-HT1A agonists) provides strong converging evidence for the anxiolytic-like characteristics of SST. Our pharmacological antagonism experiments with bicuculline further suggest that the anxiolytic effect of SST may be attributable to the interaction of SST with GABA, whereas the antidepressant-like effect of SST may be GABA-independent. In addition to contributing to the current understanding of the role of neuropeptides in mood and emotion, these findings support a clinical role for SST (or its analogues) in the treatment of anxiety and depression.
生长抑素（SST）是一种环状多肽，可抑制多种调节激素（如生长激素、胰岛素、胰高血糖素、促甲状腺激素）的释放。此外，SST在中枢神经系统中广泛分布，既作为神经递质，又作为其他神经递质系统的神经调质发挥作用。然而，尽管SST在边缘区域广泛表达，且与γ-氨基丁酸（GABA，一种先前被认为与情绪有关的神经递质）共定位，但SST对焦虑和抑郁的影响尚未得到研究。通过对大鼠进行脑室内注射，我们首次证明，SST在高架十字迷宫试验和强迫游泳试验中分别具有抗焦虑和抗抑郁样作用。此外，通过对乌拉坦麻醉的大鼠进行网状刺激诱发的海马θ活动的局部场电位记录，我们还表明，应用SST抑制θ频率的方式与地西泮相似。这种所有抗焦虑药物（即苯二氮䓬类、选择性5-羟色胺再摄取抑制剂、5-羟色胺1A激动剂）共有的神经生理特征，为SST的抗焦虑样特性提供了强有力的汇聚证据。我们用荷包牡丹碱进行的药理拮抗实验进一步表明，SST的抗焦虑作用可能归因于SST与GABA的相互作用，而SST的抗抑郁样作用可能与GABA无关。除了有助于当前对神经肽在情绪和情感中作用的理解外，这些发现还支持SST（或其类似物）在焦虑和抑郁治疗中的临床作用。
