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

• Published in: Journal of psychopharmacology (Oxford) Vol. 33; no. 6; pp. 737 - 747
• Main Authors: Millón, Carmelo, Flores-Burgess, Antonio, Gago, Belén, Alén, Francisco, Orio, Laura, García-Durán, Laura, Narváez, José A, Fuxe, Kjell, Santín, Luis, Díaz-Cabiale, Zaida
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-06-2019; Sage Publications Ltd
• Subjects: c-Fos protein; Dopamine; Dopamine D1 receptors; Dopamine D2 receptors; Dopamine D3 receptors; Dopamine D5 receptors; Dopamine receptors; Dopamine transporter; Emission analysis; Fos gene; Galanin; Galanin receptors; Gene expression; Hedonic response; Immunoreactivity; Limbic system; Medical treatment; Medicin och hälsovetenskap; Mesolimbic system; Mood; Nucleus accumbens; Operant conditioning; Phenotypes; Positron emission tomography; Reinforcement; Saccharin; Self-administration; Sucrose; Sugar; Tomography; Urine; reward circuit; depression; Galanin; galanin N-terminal fragment (1-15); dopamine; anhedonia
• ISSN: 0269-8811; 1461-7285; 1461-7285
• DOI: 10.1177/0269881119844188

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.