Journal
NEUROSCIENCE
Volume 154, Issue 4, Pages 1178-1186Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2008.04.005
Keywords
stress resilience; learned helplessness; 5-HT; dorsal raphe nucleus; microdialysis; picrotoxin
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Funding
- NIMH NIH HHS [MH 50479, R37 MH050479, R01 MH050479-16, R01 MH050479] Funding Source: Medline
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The degree of behavioral control that an organism has over a stressor determines the behavioral and neurochemical sequelae of the stressor, with the presence of control preventing the typical outcomes that occur when the stressor is uncontrollable (e.g. failure to learn, exaggerated fear, dorsal raphe nucleus (DRN) 5-HT activation). Furthermore, an experience with a controllable stressor blocks the consequences of later uncontrollable stressors (immunization). These effects of control have been argued to be mediated by control-induced activation of ventral medial prefrontal cortex (mPFCv) output to the DRN. The experiments that have led to this interpretation have all involved the inactivation of the mPFCv with muscimol, showing that inactivation during the stressor eliminates the stressor-resistance produced by control, with the controllable stressor now acting as if it were uncontrollable. The present experiments in rats employed the opposite strategy, activating the mPFCv during the stressor. mPFCv microinjection of picrotoxin during the stressor eliminated the DRN 5-HT activation that normally occurs during the uncontrollable stressor, as well as the escape learning deficit and exaggerated fear that normally follows uncontrollable stress. Furthermore, mPFCv activation during an initial exposure to an uncontrollable stressor led the uncontrollable stressor to produce behavioral and neurochemical immunization when the subjects were later exposed to an uncontrollable stressor. That is, the conjoint activation of the mPFCv and exposure to an uncontrollable stressor led the uncontrollable stressor to act as if it were controllable. These results provide strong support for the argument that behavioral control produced stress-resistance by activating the mPFCv. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.
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