Social phobia - Neurophysiological correlates

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

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. ↥ ↥
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. ↥
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. ↥
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. ↥
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. ↥
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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Social phobia - Neurophysiological correlates