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Review
. 2025;23(3):295-309.
doi: 10.2174/1570159X23666241003125019.

A New Augmentation Strategy against Depression Combining SSRIs and the N-terminal Fragment of Galanin (1-15)

Antonio Flores-Burgess  1 , Carmelo Millon  1 , Noelia Cantero-Garcia  1 , Juan Pedro Pineda-Gomez  1 , Marta Flores-Gomez  1 , Zaida Diaz-Cabiale  1
Affiliations
Review

A New Augmentation Strategy against Depression Combining SSRIs and the N-terminal Fragment of Galanin (1-15)

Antonio Flores-Burgess et al. Curr Neuropharmacol. 2025.

Abstract

Depression is one of the most disabling mental disorders, with the second highest social burden; its prevalence has grown by more than 27% in recent years, affecting 246 million in 2021. Despite the wide range of antidepressants available, more than 50% of patients show treatment-resistant depression. In this review, we summarized the progress in developing a new augmentation strategy based on combining the N-terminal fragment of Galanin (1-15) and SSRI-type antidepressants in animal models.

Keywords: Depression; GAL(1-15); SSRIs; animal models; antidepressants.; augmentation therapy.

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Conflict of interest statement

The authors declare no conflict of interest, financial or otherwise.

Figures

Fig. (1)
Fig. (1)
Schematic representation of GAL(1-15) neurochemical effects on serotoninergic (up) and dopaminergic (down) systems mediated by the proposed GALR1-GALR2 heterodimer. GAL(1-15) induces a decrease in the serotonin (5-HT) liberation in RN33B cells and modifies the binding characteristics of 5HT1AR in DR and the dorsal hippocampus (d-Hipo). The fragment modifies the mRNA expression of different dopaminergic system elements in the Ventral tegmental area (VTA) and Nucleus accumbens (NAc). GAL(1-15) also decreases the tyrosine hydroxylase immunoreactivity (TH-IR) in the striatum.
Fig. (2)
Fig. (2)
Schematic representation of the molecular mechanics underlying the GAL(1-15)+FLX effects in näive (up) and bulbectomized animals (OBX) (down). The receptor complex GALR1/GALR2/5HT1AR is proposed as the molecular complex where 5HT1AR binding properties are modified differently in the Prefrontal cortex (CPF) and dorsal hippocampus (d-Hipo). The effects in the HPA axis is also described.
Fig. (3)
Fig. (3)
Schematic representation of the proposed neural networks after Principal component analysis (PCA) from the data obtained from the c-Fos immunoreactivity (c-Fos IR) in the Prefrontal cortex (PFC), Dentate gyrus of the dorsal hippocampus (DG) and Lateral habenula (LHb); and double immunoreactivity to c-Fos + Tyrosine hydroxilase (c-Fos/TH IR) in the Ventral tegmental area (VTA) and c-Fos + serotonin (c-Fos/5-HT IR) in the dorsal raphe (DR). The coadministration of GAL(1-15) + Escitalopram (ESC) induces an increase of the c-Fos IR in PFC, DG, and LHb compared to the control group and also an increase of c-Fos/TH IR and c-Fos/5-HT IR in VTA and DR respectively.
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