The Combination of Galanin (1–15) and Escitalopram in Rats Suggests a New Strategy for Alcohol Use Disorder Comorbidity with Depression
Noelia Cantero-García,
Antonio Flores-Burgess,
David Ladrón de Guevara-Miranda,
Antonia Serrano,
Laura García-Durán,
Araceli Puigcerver,
Kjell Fuxe,
José Ángel Narváez,
Luis Javier Santín,
Zaida Díaz-Cabiale,
Carmelo Millón
Affiliations
Noelia Cantero-García
Facultad de Medicina, Instituto de Investigación Biomédica de Málaga, Campus de Teatinos s/n, Universidad de Málaga, 29071 Málaga, Spain
Antonio Flores-Burgess
Facultad de Medicina, Instituto de Investigación Biomédica de Málaga, Campus de Teatinos s/n, Universidad de Málaga, 29071 Málaga, Spain
David Ladrón de Guevara-Miranda
Facultad de Psicología, Instituto de Investigación Biomédica de Málaga, Campus de Teatinos s/n, Universidad de Málaga, 29071 Málaga, Spain
Antonia Serrano
Unidad de Gestión Clínica de Salud Mental e Instituto de Investigación Biomédica de Málaga, Hospital Regional Universitario de Málaga, 29010 Málaga, Spain
Laura García-Durán
Facultad de Medicina, Instituto de Investigación Biomédica de Málaga, Campus de Teatinos s/n, Universidad de Málaga, 29071 Málaga, Spain
Araceli Puigcerver
Facultad de Psicología, Instituto de Investigación Biomédica de Málaga, Campus de Teatinos s/n, Universidad de Málaga, 29071 Málaga, Spain
Kjell Fuxe
Department of Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden
José Ángel Narváez
Facultad de Medicina, Instituto de Investigación Biomédica de Málaga, Campus de Teatinos s/n, Universidad de Málaga, 29071 Málaga, Spain
Luis Javier Santín
Facultad de Psicología, Instituto de Investigación Biomédica de Málaga, Campus de Teatinos s/n, Universidad de Málaga, 29071 Málaga, Spain
Zaida Díaz-Cabiale
Facultad de Medicina, Instituto de Investigación Biomédica de Málaga, Campus de Teatinos s/n, Universidad de Málaga, 29071 Málaga, Spain
Carmelo Millón
Facultad de Medicina, Instituto de Investigación Biomédica de Málaga, Campus de Teatinos s/n, Universidad de Málaga, 29071 Málaga, Spain
Alcohol use disorder (AUD) is highly prevalent, and over 50% of AUD patients also suffer major depressive disorders. Selective 5-HT reuptake inhibitors (SSRIs) can reduce rodent ethanol drinking but exert modest clinical efficacy in alcoholic individuals. Finding new pharmacological strategies that could modulate alcohol consumption and depression is necessary. We have analyzed the effect of Galanin (1–15) [GAL(1–15)] on escitalopram (ESC)-mediated effect in alcohol consumption using the alcohol self-administration test, the nuclei involved in the effect, and whether GAL(1–15) + ESC modulated the response in despair or anxiety tests in animals under chronic alcohol intake. GAL(1–15) + ESC combination substantially reduced alcohol intake in the alcohol self-administration test and, moreover, enhanced the reduction of reward capacity of ESC on different reinforcers such as sucrose or saccharine. GAL(1–15) + ESC coadministration significantly decreases the number of C-Fos-IR TH cell bodies in the VTA, and PCA analysis suggests that one functional network, including VTA, RMTg and DR, is involved in these effects. Significantly in rats with chronic alcohol consumption, GAL(1–15) reversed adverse ESC-mediated effects in the depression-related behavioural test and forced swimming test. The results open up the possibility of using GAL(1–15) in combination with the SSRI Escitalopram as a novel strategy in AUD comorbidity with depression.
