Posted by jrbecker on February 13, 2006, at 18:30:00
In reply to Interesting article in Science about how changes, posted by Pfinstegg on February 13, 2006, at 18:25:20
> in the dopamine reward pathways of the brain are altered in depression, PTSD and social withdrawal. (Science, Vol 311, 10 February, 2006).
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> This article describes how "bullied mice" (those subjected to a larger, aggressive mouse) developed symptoms of social defeat, mediated by BDNF in the dopaminergic mesolimbic pathways- the "reward system". The presence of BDNF was essential for this learned defeat and social withdrawal. Either knocking out BDNF in this pathway, or administering fluoxetine, prevented this from happening. Up until now, attention has focussed on preserving BDNF and serotonin in the hippocampus and other nearby areas, in the treatment of these symptoms, which many antidepressants, including fluoxetine, are thought to do.
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> I thought it was interesting that the dopaminergic pathways are emerging as important areas in depression and PTSD, and also that while BDNF is considered important in maintaining a healthy hippocampus, and is vital to memory and new learning, it could be one of the neurotransmitters in learned social defeat and depression
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> I have always been aware that absence of a sense of reward is one of the biggest difficulties when one is depressed. But I've also noticed, from personal experience and from many posts here, that long-term use of SSRIs and SNRIs can make that symptom even worse, even though, according to this article, it is supposed to preserve the sense of reward in social interactions despite social stress.
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yes, here's another article from 2003 that also underlines the fact that neurogenesis in the VTA >negatively< impacts mood..Biol Psychiatry. 2003 Nov 15;54(10):994-1005.
Brain-derived neurotrophic factor in the ventral midbrain-nucleus accumbens pathway: a role in depression.
Eisch AJ, Bolanos CA, de Wit J, Simonak RD, Pudiak CM, Barrot M, Verhaagen J, Nestler EJ.
Department of Psychiatry, The University of Texas Southwestern Medical Center, Texas, Dallas 75390-9070, USA.
BACKGROUND: Previous work has shown that brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase receptor B (TrkB), are involved in appetitive behavior. Here we show that BDNF in the ventral tegmental area-nucleus accumbens (VTA-NAc) pathway is also involved in the development of a depression-like phenotype. METHODS: Brain-derived neurotrophic factor signaling in the VTA-NAc pathway was altered in two complementary ways. One group of rats received intra-VTA infusion of vehicle or BDNF for 1 week. A second group of rats received intra-NAc injections of vehicle or adeno-associated viral vectors encoding full-length (TrkB.FL) or truncated (TrkB.T1) TrkB; the latter is kinase deficient and serves as a dominant-negative receptor. Rats were examined in the forced swim test and other behavioral tests. RESULTS: Intra-VTA infusions of BDNF resulted in 57% shorter latency to immobility relative to control animals, a depression-like effect. Intra-NAc injections of TrkB.T1 resulted in and almost fivefold longer latency to immobility relative to TrkB.FL and control animals, an antidepressant-like effect. No effect on anxiety-like behaviors or locomotion was seen. CONCLUSIONS: These data suggest that BDNF action in the VTA-NAc pathway might be related to development of a depression-like phenotype. This interpretation is intriguing in that it suggests a role for BDNF in the VTA-NAc that is opposite of the proposed role for BDNF in the hippocampus.
PMID: 14625141 [PubMed - indexed for MEDLINE]
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