Altar C A
Mayland Research Laboratories, Otsuka America Pharmaceutical, Rockville 20850, USA.
Trends Pharmacol Sci. 1999 Feb;20(2):59-61. doi: 10.1016/s0165-6147(99)01309-7.
Exogenous delivery of the neurotrophic factors, brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3), promotes the function, sprouting and regrowth of 5-HT-containing neurones in the brains of adult rats. Similar infusions of BDNF into the dorsal raphe nucleus produce an antidepressant effect, as evaluated by several 'learned helplessness' paradigms. Environmental stressors such as immobilization induce depression and decrease BDNF mRNA. Antidepressants increase BDNF mRNA in the brain, via 5-HT2A and beta-adrenoceptor subtypes and prevent the stress-induced decreases in BDNF mRNA. In this article, Tony Altar discusses how existing treatments of depression might work by increasing endogenous brain levels of BDNF or NT-3, which in turn could promote monoamine-containing neurone growth and function. Drugs that selectively stimulate the production of neurotrophins could represent a new generation of antidepressants.
外源性递送神经营养因子、脑源性神经营养因子（BDNF）或神经营养素-3（NT-3），可促进成年大鼠脑中含5-羟色胺（5-HT）神经元的功能、发芽和再生。通过几种“习得性无助”范式评估，向中缝背核类似地注入BDNF会产生抗抑郁作用。诸如固定等环境应激源会诱发抑郁并降低BDNF mRNA水平。抗抑郁药通过5-HT2A和β-肾上腺素能受体亚型增加脑中的BDNF mRNA，并防止应激诱导的BDNF mRNA降低。在本文中，托尼·阿尔塔尔讨论了现有的抑郁症治疗方法可能如何通过增加内源性脑BDNF或NT-3水平来发挥作用，而这反过来又可以促进含单胺神经元的生长和功能。选择性刺激神经营养素产生的药物可能代表新一代抗抑郁药。
