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Eur J Neurosci. 2018 Apr;47(8):959-967. doi: 10.1111/ejn.13833. Epub 2018 Feb 5.

Behavioural and neural sequelae of stressor exposure are not modulated by controllability in females.

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Department of Psychology and Neuroscience, University of Colorado Boulder, UCB 345/Muenzinger D244, Boulder, CO, 80309-0345, USA.
Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.


The degree of behavioural control that an organism has over a stressor is a potent modulator of the stressor's impact; controllable stressors produce none of the neurochemical and behavioural sequelae that occur if the stressor is uncontrollable. Research demonstrating the importance of control and the neural mechanisms responsible has been conducted almost entirely with male rats. It is unknown if behavioural control is stress blunting in females, and whether or not a similar resilience circuitry is engaged. Female rats were exposed to controllable, yoked uncontrollable or no tailshock. In separate experiments, behavioural (juvenile social exploration, fear and shuttle box escape) and neurochemical (activation of dorsal raphe serotonin and dorsal raphe-projecting prelimbic neurons) outcomes, which are sensitive to the dimension of control in males, were assessed. Despite successful acquisition of the controlling response, behavioural control did not mitigate dorsal raphe serotonergic activation and behavioural outcomes induced by tailshock, as it does in males. Moreover, behavioural control failed to selectively engage prelimbic cells that project to the dorsal raphe as in males. Pharmacological activation of the prelimbic cortex restored the stress-buffering effects of control. Collectively, the data demonstrate stressor controllability phenomena are absent in females and that the protective prelimbic circuitry is present but not engaged. Reduced benefit from coping responses may represent a novel approach for understanding differential sex prevalence in stress-related psychiatric disorders.


anxiety; learned helplessness; medial prefrontal cortex; rat; serotonin

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