Neurotrophins and depression.
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.
Altar
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Mayland Research Laboratories, Otsuka America Pharmaceutical, Rockville 20850, USA.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism* / Q000628:therapy; D004565:Electroconvulsive Therapy; D006380:Helplessness, Learned; D006801:Humans; D009414:Nerve Growth Factors / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D020933:Neurotrophin 3; D012333:RNA, Messenger / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D012333:RNA, Messenger; D012701:Serotonin