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© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Selective 5-HT reuptake inhibitor antidepressants (SSRIs) are the first choice in major depressive disorder (MDD), but 50% of affected patients do not show improvement. Galanin(1-15) [GAL(1-15)] enhanced Fluoxetine antidepressant-like effects in an animal model of depression, the olfactory bulbectomy (OBX); however, further detailed analysis of GAL(1-15) effects as augmentation treatment in OBX rats are needed. In OBX rats, we analysed the effect of GAL(1–15) on Escitalopram (ESC)-mediated responses in behavioural tests related to despair. We studied whether GAL(1–15) effects involved 5-HT1AR using an in vivo model siRNA 5-HT1A knockdown rats. Moreover, we analysed by immunohistochemistry the expression of the immediate-early gene c-Fos (c-Fos IR) after the administration of GAL(1-15)+ESC in OBX rats in several nuclei involved in MDD. GAL(1-15) enhances the antidepressant-like effects of ESC, and the GALR2 antagonist M871 blocked GAL(1-15) mediated actions. The downregulation of 5-HT1AR by siRNA was sufficient to block GAL(1-15) effects. Our immunohistochemistry and principal component analysis (PCA) analysis suggest that two functional networks are involved in these effects; one includes the lateral (LHb) and medial (mHb) habenula, dorsal raphe (DR) and ventral tegmental area (VTA), and the other consists of the dentate gyrus (DG), and prefrontal cortex (PFC). The results open up the possibility of using GAL(1-15) in combination with SSRIs as a novel strategy for treating MDD.

Details

Title
Galanin(1-15) Potentiates the Antidepressant-like Effects Induced by Escitalopram in a Rat Model of Depression
Author
García-Durán, Laura 1   VIAFID ORCID Logo  ; Flores-Burgess, Antonio 1 ; Cantero-García, Noelia 1 ; Puigcerver, Araceli 2 ; Narváez, José Ángel 1 ; Fuxe, Kjell 3   VIAFID ORCID Logo  ; Santín, Luis 2   VIAFID ORCID Logo  ; Millón, Carmelo 1   VIAFID ORCID Logo  ; Díaz-Cabiale, Zaida 1   VIAFID ORCID Logo 

 Faculty of Medicine, Institute of Biomedical Research of Malaga, Campus de Teatinos s/n, University of Malaga, 29071 Malaga, Spain; [email protected] (L.G.-D.); [email protected] (A.F.-B.); [email protected] (N.C.-G.); [email protected] (J.Á.N.) 
 Faculty of Psychology, Institute of Biomedical Research of Malaga, Campus de Teatinos s/n, University of Málaga, 29071 Malaga, Spain; [email protected] (A.P.); [email protected] (L.S.) 
 Department of Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden; [email protected] 
First page
10848
Publication year
2021
Publication date
2021
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2581026509
Copyright
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.