Social defeat stress is an ethologically salient stressor which activates dopaminergic areas and, when experienced repeatedly, has long-term effects on dopaminergic function and related behavior. The mechanism for these long-lasting consequences remains unclear. A potential candidate for mediating these effects is brain-derived neurotrophic factor (BDNF), a neurotrophin involved in synaptic plasticity and displaying alterations in dopaminergic regions in response to various types of stress. In this study, we sought to determine whether repeated social defeat stress altered BDNF mRNA and protein expression in dopaminergic brain regions either immediately after the last stress exposure or four weeks later. Male Sprague-Dawley rats were subjected to social defeat stress consisting of brief confrontation with an aggressive male rat every third day for 10 days; control rats were handled according to the same schedule. Animals were euthanized either 2 h or 28 days after the last stress or handling episode. Our results show that 2 h after stress, BDNF protein and mRNA expression increased in the medial prefrontal cortex. At this time-point, BDNF mRNA increased in the amygdala and protein expression increased in the substantia nigra. Twenty-eight days after stress, BDNF protein and mRNA expression were elevated in the medial amygdala and ventral tegmental area. Given the role of BDNF in neural plasticity, BDNF alterations that are long-lasting may be significant for neural adaptations to social stress. The dynamic nature of BDNF expression in dopaminergic brain regions in response to repeated social stress may therefore have implications for lasting neurochemical and behavioral changes related to dopaminergic function.
KeywordsMesolimbic; ventral tegmental area; prefrontal cortex; amygdala; dopamine; neurotrophin Social defeat stress is an ethologically salient stressor which provides a relevant model to investigate the etiology of stress-related disorders in humans (Koolhaas et al., 1997;Koolhaas et al., 1999 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. is sufficient to alter behaviors such as exploratory activity and sensitivity to other stressors for several weeks (Koolhaas et al., 1999).
NIH Public AccessVarious types of stressors can dramatically alter neurochemistry specifically within the mesocorticolimbic dopamine circuit (Fadda et al., 1978;Dunn and File, 1983;Deutch et al., 1985;Louilot et al., 1986;Abercrombie et al., 1989;Imperato et al., 1992;Tidey and Miczek, 1996;Nikulina et al., 1998Nikulina et al., , 2001Bland et al., 2005;, which mediates general rewa...