BUSCADOR RECOLECTA

Collection of data published in the article: https://hdl.handle.net/10630/23528, Spanish Ministry of Economy SAF2016-79008-P, PSI2017-82604-R, PID2020- 114392RB-I00, PDC2021-121566-I0. Junta de Andalucia UMA18-FEDERJA-008, P20_00026, PI-0083-2019

Alcohol Use Disorder (AUD) is among the most prevalent mental illnesses, and due to the low efficacy of the current medication, it is essential to find new biological targets that could modulate alcohol consumption. Since Galanin (1− 15) [GAL(1− 15)] produces a loss of motivational behaviour by an artificial reinforcer and decreases the preference an alcohol consumption in a voluntary alcohol intake, we have studied the role of GAL(1− 15) in alcohol-seekingbehaviourandtheinvolvementofthecorticomesolimbicsystemaswellastheroleofGAL(1− 15) in context-induced alcohol relapse. In rats, we have studied GAL(1− 15)-effects on alcohol-seeking in self- administration, in fixed-ratio (FR1) and progressive-ratio (PR), and the involvement of GAL receptors using siRNA GALR1 or GALR2 knockdown animals. We have analysed the transcriptional changes of C-Fos, dopamine receptors, GAL receptors and 5HT1A receptors in the corticomesolimbic system. Also, we have examined the effect of GAL(1− 15) in context-induced alcohol relapse. GAL(1− 15) substantially reduced alcohol-seeking behaviour in the operant self-administration model in an FR1 protocol and at the breaking point in a PR schedule. GALR1and GALR2 were involved in these effects, as indicated by the analysis by GALR2 antagonist and GALR1 and GALR2 knockdown animals. Notably, the mechanism of GAL(1− 15)-mediated actions involved changes in C-Fos, Dopamine receptors and 5HT1A expression in the ventral tegmental area, accumbens nucleus and prefrontal cortex. Significantly, GAL(1− 15) reduced the context-induced alcohol relapse. These results open up the possibility to use GAL(1− 15) as a novel strategy in AUD., This work was supported by grants awarded by Spanish Ministry of Economy PID2020-114392RB-100, PDC2021-121566-100 and by Junta de Andalucía P20-00026-R and PI-0083-2019

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., This work was supported by grants awarded by Spanish Ministry of Economy PID2020- 114392RB-100, PDC2021-121566-100 and by Junta de Andalucía P20-00026-R and PI-0083-2019.