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CGRP in a gene–environment interaction model for depression: effects of antidepressant treatment

Published online by Cambridge University Press:  04 December 2018

Francesco Angelucci ,
Bart A Ellenbroek ,
Aram El Khoury  and
Aleksander A. Mathé
Francesco Angelucci
Affiliation:
Memory Clinic, Department of Neurology, Charles University, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic
Bart A Ellenbroek*
Affiliation:
Behavioural Neurogenetics Group, School of Psychology, Victoria University of Wellington, New Zealand
Aram El Khoury
Affiliation:
Institution of Clinical Neuroscience, Division of Psychiatry, Karolinska Institutet, S-171 77Sweden
Aleksander A. Mathé
Affiliation:
Institution of Clinical Neuroscience, Division of Psychiatry, Karolinska Institutet, S-171 77Sweden
*
Author for correspondence: Bart Ellenbroek, Victoria University Wellington, School of Psychology, Behavioural Neurogenetics Group, Wellington 6041, New Zealand. Tel: +61 4 463 6159; E-mail: bart.ellenbroek@vuw.ac.nz
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Abstract

Objective

Genetic and environmental factors interact in the development of major depressive disorder (MDD). While neurobiological correlates have only partially been elucidated, altered levels of calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) in animal models and in the cerebrospinal fluid of depressed patients were reported, suggesting that CGRP may be involved in the pathophysiology and/or be a trait marker of MDD. However, changes in CGRP brain levels resulting from interactions between genetic and environmental risk factors and the response to antidepressant treatment have not been explored.

Methods

We therefore superimposed maternal separation (MS) onto a genetic rat model (Flinders-sensitive and -resistant lines, FSL/FRL) of depression, treated these rats with antidepressants (escitalopram and nortriptyline) and measured CGRP-LI in selected brain regions.

Results

CGRP was elevated in the frontal cortex, hippocampus and amygdala (but not in the hypothalamus) of FSL rats. However, MS did not significantly alter levels of this peptide. Likewise, there were no significant interactions between the genetic and environmental factors. Most importantly, neither escitalopram nor nortriptyline significantly altered brain CGRP levels.

Conclusion

Our data demonstrate that increased brain levels of CGRP are present in a well-established rat model of depression. Given that antidepressants have virtually no effect on the brain level of this peptide, our study indicates that further research is needed to evaluate the functional role of CGRP in the FSL model for depression.

Keywords

calcitonin gene-related peptideescitalopramFlinders-sensitive linematernal deprivationnortriptyline
Type
Original Article
Information
Acta Neuropsychiatrica , Volume 31 , Issue 2 , April 2019 , pp. 93 - 99
Copyright
© Scandinavian College of Neuropsychopharmacology 2018 

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