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Changes in Gene Expression in the Locus Coeruleus-Amygdala Circuitry in Inhibitory Avoidance PTSD Model

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Abstract

The locus coeruleus (LC)-amygdala circuit is implicated in playing a key role in responses to emotionally arousing stimuli and in the manifestation of post-traumatic stress disorder (PTSD). Here, we examined changes in gene expression of a number of important mediators of the LC-amygdala circuitry in the inhibition avoidance model of PTSD. After testing for basal acoustic startle response (ASR), rats were exposed to a severe footshock (1.5 mA for 10 s) in the inhibitory avoidance apparatus. They were given contextual situational reminders every 5 day for 25 days. Controls were treated identically but with the footshock inactivated. Animals were re-tested on second ASR and decapitated 1 h later. The shock group had enhanced hyperarousal and several changes in gene expression compared to controls. In the LC, mRNA levels of norepinephrine (NE) biosynthetic enzymes (TH, DBH), NE transporter (NET), NPY receptors (Y1R, Y2R), and CB1 receptor of endocannabinoid system were elevated. In the basolateral amygdala (BLA), there were marked reductions in gene expression for CB1, and especially Y1R, with rise for corticotropin-releasing hormone (CRH) system (CRH, CRH receptor 1), and no significant changes in the central amygdala. Our results suggest a fast forward mechanism in the LC-amygdala circuitry in the shock group.

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Acknowledgements

This investigation was supported with funds from the NYMC/Touro Bridge Funding Program (to ES) and the Israel Science Foundation Grant 572/12 (to IA).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Basic Sciences Building, New York Medical College, Valhalla, NY, 10595, USA

    Esther L. Sabban, Lidia I. Serova & Elizabeth Newman

  2. Department of Psychology, University of Haifa, 3498838, Haifa, Israel

    Nurit Aisenberg & Irit Akirav

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  1. Esther L. Sabban
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  2. Lidia I. Serova
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  3. Elizabeth Newman
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  4. Nurit Aisenberg
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  5. Irit Akirav
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Contributions

Esther L. Sabban helped to plan experiment, discussed results, and wrote manuscript; Lidia I. Serova performed qPCR for LC, analyzed and discussed data, and participated in writing manuscript; Elizabeth Newman performed qPCR for BLA and CeA, analyzed data; Nurit Aisenberg performed the animal manipulations and isolation of the brain tissue; Irit Akirav planned the experiment, discussed data, and participated in writing the manuscript.

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Correspondence to Esther L. Sabban.

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Sabban, E.L., Serova, L.I., Newman, E. et al. Changes in Gene Expression in the Locus Coeruleus-Amygdala Circuitry in Inhibitory Avoidance PTSD Model. Cell Mol Neurobiol 38, 273–280 (2018). https://doi.org/10.1007/s10571-017-0548-3

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