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Prior evidence implicates serotonin and SERT in anxiety and stress responses. Some studies have shown that BDNF supports serotonergic neuronal development, leading to our hypothesis that reduced BDNF availability during development might exaggerate the consequences of absent SERT function. In the present study, brain serotonin and 5\u2010hydroxyindol acetic acid concentrations in male sb mice were significantly reduced in the hippocampus and hypothalamus compared with wild\u2010type control SB mice, BDNF\u2010deficient Sb mice, and serotonin transporter knockout sB mice. The sb mice had significantly increased anxiety\u2010like behaviors compared with SB, Sb, and sB mice as measured on the elevated plus maze test. These sb mice also had significantly greater increases in plasma adrenocorticotrophic hormone than mice with other genotypes after a stressful stimulus. Analysis of neuronal morphology showed that hypothalamic and hippocampal neurons exhibited 25\u201330% reductions in dendrites in sb mice compared with SB control mice. These findings support the hypothesis that genetic changes in BDNF expression interact with serotonin and other circuits that modulate anxiety and stress\u2010related behaviors. Thus, this double\u2010mutant mouse model should prove valuable in studying other gene \u00d7 gene consequences for brain plasticity as well as in evaluating epistatic interactions of BDNF and serotonin transporter gene polymorphisms in neuropsychiatric disorders. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jnr.20410","type":"journal-article","created":{"date-parts":[[2005,1,25]],"date-time":"2005-01-25T19:17:23Z","timestamp":1106680643000},"page":"756-771","source":"Crossref","is-referenced-by-count":104,"title":["Loss of brain\u2010derived neurotrophic factor gene allele exacerbates brain monoamine deficiencies and increases stress abnormalities of serotonin transporter knockout mice"],"prefix":"10.1002","volume":"79","author":[{"given":"Renee F.","family":"Ren\u2010Patterson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren 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