ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Intranasal Galanin (1-15) modulates alcohol self-administration and depressive-like behavior in rats and shows a favorable safety profile
Provisionally accepted
Noelia Cantero-García1
Antonio Flores-Burgess1
Marta Flores-Gómez1Juan Pedro Pineda-Gómez1
Carmen Ramos2
Caridad Díaz2
Carmelo Millón1*
Zaida Diaz Cabiale1- 1University of Malaga, Málaga, Spain
- 2Fundacion Centro de Excelencia en Investigacion de Medicamentos Innovadores en Andalucia, Granada, Spain
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Galanin is a neuropeptide in the central nervous system that regulates mood and alcohol consumption. Its N-terminal fragment, Galanin(1-15) [GAL(1-15)], has demonstrated specific behavioral effects, enhancing the efficacy of selective serotonin reuptake inhibitors (SSRIs) and reducing ethanol intake and alcohol self-administration in preclinical models. Additionally, GAL(1-15) combined with SSRIs decreases alcohol self-administration and depressive symptoms in a comorbid alcoholism-depression model. These findings suggest potential applications in the treatment of depression and alcohol use disorders. Given its therapeutic potential, evaluating the translational aspects and safety of GAL(1-15) is essential for clinical development. This study investigated the intranasal administration of GAL(1-15), assessing its effects on depression-related behavior in the Forced Swim Test (FST) and alcohol self-administraation in an operant self-administration model. To determine its safety profile, we evaluated GAL(1-15) for cardiotoxicity (hERG channel inhibition), genotoxicity (micronucleus formation), and drug interactions (CYP450 inhibition). Results showed that intranasal GAL(1-15) exhibited a prodepressant effect, as previously demonstrated with its ICV administration. Furthermore, intranasal GAL(1-15) effectively reduced alcohol consumption. In vitro safety assessments revealed no adverse effects on cardiac function or genotoxicity at the concentrations studied, with minimal interaction with CYP450 enzymes, supporting its suitability for drug development. In conclusion, intranasal administration of GAL(1–15) represents a promising candidate for clinical trials due to its favorable safety profile and therapeutic potential. Its use appears particularly suitable as a standalone treatment for alcohol use disorder and, when combined with SSRIs, as a potential therapy for depressive disorders.
Keywords: Galanin, intranasal, Safety profile, Depression, Alcohol disorders
Received: 06 Oct 2025; Accepted: 10 Nov 2025.
Copyright: © 2025 Cantero-García, Flores-Burgess, Flores-Gómez, Pineda-Gómez, Ramos, Díaz, Millón and Diaz Cabiale. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Carmelo Millón, carmelomp@uma.es
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