Chronic desipramine prevents acute stress-induced reorganization of medial prefrontal cortex architecture by blocking glutamate vesicle accumulation and excitatory synapse increase

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While a clear negative influence of chronic exposure to stressful experiences has been repeatedly demonstrated, the outcome of acute stress on key brain regions has only just started to be elucidated. Although it has been proposed that acute stress may produce enhancement of brain plasticity and that antidepressants may prevent such changes, we still lack ultrastructural evidence that acute stress-induced changes in neurotransmitter physiology are coupled with structural synaptic modifications. Rats were pretreated chronically (14 days) with desipramine (DMI; 10 mg/kg) and then subjected to acute foot-shock (FS)-stress. By means of serial section electron microscopy, the structural remodeling of medial prefrontal cortex (mPFC) glutamate synapses was assessed soon after acute stressor cessation and stress hormone levels were measured. FS-stress induced a remarkable increase in the number of docked vesicles and small excitatory synapses, partially and strongly prevented by DMI pretreatment, respectively. Acute stress-induced corticosterone elevation was not affected by drug treatment. Since DMI pretreatment prevented the stress-induced structural plasticity but not the hormone level increase, we hypothesize that the preventing action of DMI is located on pathways downstream of this process and/or other pathways. Moreover, because enhancement of glutamate system remodeling may contribute to overexcitation dysfunctions, this aspect could represent a crucial component in the pathophysiology of stress-related disorders.

Original languageEnglish
JournalInternational Journal of Neuropsychopharmacology
ISSN1461-1457
DOIs
Publication statusPublished - 13 Dec 2014

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