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Neurophysiological correlates of social phobia.

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Neurophysiological correlates of social phobia.

Mice that experienced repeated aggression by conspecifics developed a lifelong social phobia. This could be remedied by:

  • Elimination of BDNF in the VTA / nucleus accumbens pathway1
  • Permanent antidepressant administration (fluoxetine)1
  • Single administration of ketamine, but less Rabastinel2
    • This also indicates the importance of BDNF in socially triggered stress

BDNF deprivation in the VTA/nucleus accumbens pathway appears to exert antidepressant effects,34 5 , whereas conversely in the hippocampus BDNF administration exerts antidepressant effects and antidepressants slowly increase BDNF in the hippocampus and ketamine rapidly increases BDNF in the hippocampus.6


  1. Berton, McClung, Dileone, Krishnan, Renthal, Russo, Graham, Tsankova, Bolanos, Rios, Monteggia, Self, Nestler (2006): Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science. 2006 Feb 10;311(5762):864-8. doi: 10.1126/science.1120972. PMID: 16469931.

  2. Yang, Zhang, Han, Yao, Yang, Ren, Ma, Chen, Hashimoto (2016): Comparison of R-ketamine and rapastinel antidepressant effects in the social defeat stress model of depression. Psychopharmacology (Berl). 2016 Oct;233(19-20):3647-57. doi: 10.1007/s00213-016-4399-2. PMID: 27488193; PMCID: PMC5021744.

  3. Wang, Fanous, Terwilliger, Bass, Hammer, Nikulina (2013): BDNF overexpression in the ventral tegmental area prolongs social defeat stress-induced cross-sensitization to amphetamine and increases ΔFosB expression in mesocorticolimbic regions of rats. Neuropsychopharmacology. 2013 Oct;38(11):2286-96. doi: 10.1038/npp.2013.130. PMID: 23689674; PMCID: PMC3773680.

  4. Eisch, Bolaños, de Wit, Simonak, Pudiak, Barrot, Verhaagen, Nestler (2003): Brain-derived neurotrophic factor in the ventral midbrain-nucleus accumbens pathway: a role in depression. Biol Psychiatry. 2003 Nov 15;54(10):994-1005. doi: 10.1016/j.biopsych.2003.08.003. PMID: 14625141.

  5. Wang, Bina, Wingard, Terwilliger, Hammer, Nikulina (2014): Knockdown of tropomyosin-related kinase B receptor expression in the nucleus accumbens shell prevents intermittent social defeat stress-induced cross-sensitization to amphetamine in rats. Eur J Neurosci. 2014 Mar;39(6):1009-1017. doi: 10.1111/ejn.12464. PMID: 24354924.

  6. Duman, Deyama, Fogaça (2021): Role of BDNF in the pathophysiology and treatment of depression: Activity-dependent effects distinguish rapid-acting antidepressants. Eur J Neurosci. 2021 Jan;53(1):126-139. doi: 10.1111/ejn.14630. PMID: 31811669; PMCID: PMC7274898. REVIEW

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