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SAGE Publications, Journal of Psychopharmacology, 6(33), p. 737-747, 2019

DOI: 10.1177/0269881119844188

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Role of the galanin N-terminal fragment (1-15) in anhedonia: Involvement of the dopaminergic mesolimbic system

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

Background: Anhedonia 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. Methods: 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. Results: 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. Conclusions: 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.