Increased amygdalar metabotropic glutamate receptor 7 mRNA in a genetic mouse model of impaired fear extinction
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Accepted Version
Date
2018-09-13
Authors
O’Connor, Richard M.
McCafferty, Cian P.
Bravo, Javier A.
Singewald, Nicolas
Holmes, Andrew
Cryan, John F.
Journal Title
Journal ISSN
Volume Title
Publisher
Springer Nature
Published Version
Abstract
Rationale: Post-traumatic stress disorder (PTSD) is a devastating anxiety-related disorder which develops subsequent to a severe psychologically traumatic event. Only ~ 9% of people who experience such a trauma develop PTSD. It is clear that a number of factors, including genetics, influence whether an individual will develop PTSD subsequent to a trauma. The 129S1/SvImJ (S1) inbred mouse strain displays poor fear extinction and may be useful to model this specific aspect of PTSD. The metabotropic glutamate receptor 7 (mGlu7 receptor) has previously been shown to be involved in cognitive processes and anxiety-like behaviour placing it in a key position to regulate fear extinction processes. We sought to compare mGlu7 receptor mRNA levels in the S1 strain with those in the robustly extinguishing C57BL/6J (B6) inbred strain using in situ hybridisation (ISH) in three brain regions associated with fear extinction: the amygdala, hippocampus and prefrontal cortex (PFC). Results: Compared to the B6 strain, S1 mice had increased mGlu7 receptor mRNA levels in the lateral amygdala (LA) and basolateral amygdala (BLA) subdivisions. An increase was also seen in the hippocampal CA1 and CA3 subregions of S1 mice. No difference in mGlu7 receptor levels were seen in the central nucleus (CeA) of the amygdala, dentate gyrus (DG) of the hippocampus or prefrontal cortex. Conclusions: These data show altered mGlu7 receptor expression in key brain regions associated with fear extinction in two different inbred mouse strains which differ markedly in their fear extinction behaviour. Altered mGlu7 receptor levels may contribute to the deficit fear extinction processes seen in fear extinction in the S1 strain.
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Keywords
mGlu7 receptor expression , Post-traumatic stress disorder , Trauma
Citation
O’Connor, R. M., McCafferty, C. P., Bravo, J. A., Singewald, N., Holmes, A. and Cryan, J. F. (2019) 'Increased amygdalar metabotropic glutamate receptor 7 mRNA in a genetic mouse model of impaired fear extinction', Psychopharmacology, 236, pp. 265-272. https://doi.org/10.1007/s00213-018-5031-4
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© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. This version of the paper has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s00213-018-5031-4