학술논문
Central administration of galanin N-terminal fragment 1-15 decreases the voluntary alcohol intake in rats.
Document Type
Journal Article
Author
Millón, Carmelo; Flores‐Burgess, Antonio; Castilla‐Ortega, Estela; Gago, Belén; García‐Fernandez, María; Serrano, Antonia; Rodriguez de Fonseca, Fernando; Narváez, José Angel; Fuxe, Kjell; Santín, Luis; Díaz‐Cabiale, Zaida; Flores-Burgess, Antonio; Castilla-Ortega, Estela; García-Fernandez, María; Díaz-Cabiale, Zaida
Source
Subject
*PROTEIN metabolism
*ANIMAL behavior
*ANIMAL experimentation
*BASAL ganglia
*CELL receptors
*CENTRAL nervous system depressants
*COMPARATIVE studies
*ALCOHOL drinking
*ETHANOL
*HUMAN locomotion
*RESEARCH methodology
*MEDICAL cooperation
*NEUROPEPTIDES
*PEPTIDES
*PROTEINS
*RATS
*RESEARCH
*SELF medication
*EVALUATION research
*INTRAVENTRICULAR injections
*PHARMACODYNAMICS
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Language
ISSN
1355-6215
Abstract
Alcohol consumption is considered a major risk factor for disease and mortality worldwide. In the absence of effective treatments in alcohol use disorders, it is important to find new biological targets that could modulate alcohol consumption. We tested the role of the N-terminal galanin fragment (1-15) [GAL(1-15)] in voluntary ethanol consumption in rats using the two-bottle choice paradigm as well as compare the effects of GAL(1-15) with the whole molecule of GAL. We describe for the first time that GAL(1-15), via central mechanisms, induces a strong reduction in preference and ethanol consumption in rats. These effects were significantly different than GAL. GAL receptor (GALR) 2 was involved in these effects, because the specific GALR2 antagonist M871 blocked GAL(1-15) mediated actions in preference and ethanol intake. Importantly, the mechanism of this action involves changes in GALR expression and also in immediate-early gene C-Fos and receptors-internalization-related gene Rab5 in the striatum. The relevance of the striatum as a target for GAL(1-15) was supported by the effect of GAL(1-15) on the locomotor activity of rats after ethanol administration. These results may give the basis for the development of novel therapeutics strategies using GAL(1-15) analogues for the treatment of alcohol use disorders in humans. [ABSTRACT FROM AUTHOR]