Millón, CarmeloFlores-Burgess, AntonioGago, BelénAlén, FranciscoOrio, LauraGarcía-Durán, LauraNarváez, José AFuxe, KjellSantín, LuisDíaz-Cabiale, Zaida2023-01-252023-01-252019-05-13http://hdl.handle.net/10668/13944Anhedonia is a core feature of depressive disorders. The galanin N-terminal fragment (1-15) plays a role in mood regulation since it induces depression and anxiogenic-like effects in rats. In this study, we analysed galanin N-terminal fragment (1-15) actions in anhedonic-like behaviours in rats using operant and non-operant tests and the areas involved with these effects. Galanin N-terminal fragment (1-15) effects were analysed in saccharin self-administration, sucrose preference, novelty-suppressed feeding and female urine sniffing tests. The areas involved in galanin N-terminal fragment (1-15)-mediated effects were studied with positron emission tomography for in vivo imaging, and we analysed the ventral tegmental area and nucleus accumbens. Galanin N-terminal fragment (1-15) had effects on the mRNA expression of the dopamine transporters Dat and Vmat2; the C-Fos gene; the dopamine receptors D1, D2, D3, D5; and the galanin receptors 1 and 2. Galanin N-terminal fragment (1-15) at a concentration of 3 nmol induced a strong anhedonia-like phenotype in all tests. The involvement of galanin receptor 2 was demonstrated with the galanin receptor 2 antagonist M871 (3 nmol). The 18F-fluorodeoxyglucose positron emission tomography images indicated the action of galanin N-terminal fragment (1-15) over several nuclei of the limbic system. Galanin N-terminal fragment (1-15)-mediated effects also involved changes in the expression of Dat, Vmat2, D3 and galanin receptors in the ventral tegmental area as well as the expression of C-Fos, D1, D2 and D3 and TH immunoreactivity in the nucleus accumbens. Our results indicated that galanin N-terminal fragment (1-15) exerts strong anhedonic-like effects and that this effect was accompanied by changes in the dopaminergic mesolimbic system. These results may provide a basis for the development of novel therapeutic strategies using galanin N-terminal fragment (1-15) analogues for the treatment of depression and reward-related diseases.enGalaninanhedoniadepressiondopaminegalanin N-terminal fragment (1-15)reward circuitAnhedoniaAnimalsBehavior, AnimalDepressionDopamineDopamine Plasma Membrane Transport ProteinsFemaleGalaninMaleNucleus AccumbensProto-Oncogene Proteins c-fosRatsRats, Sprague-DawleyReceptors, DopamineVentral Tegmental AreaVesicular Monoamine Transport Proteinsresearch article31081442open access10.1177/02698811198441881461-7285https://riuma.uma.es/xmlui/bitstream/10630/22797/1/GAL15-anhedonia.pdf