Document Detail

A role for galanin in antidepressant actions with a focus on the dorsal raphe nucleus.
MedLine Citation:
PMID:  15647369     Owner:  NLM     Status:  MEDLINE    
Selective serotonin reuptake inhibitors, such as fluoxetine (FLX), are the most commonly used drugs in the treatment of major depression. However, there is a limited understanding of their molecular mechanism of action. Although the acute effect of selective serotonin reuptake inhibitors in elevating synaptic serotonin concentrations is well known, the clinical amelioration of depressive symptoms requires 14-21 days of treatment, suggesting that numerous other rearrangements of function in the CNS must take place. In the present study, we demonstrated that 14 days of FLX treatment up-regulated galanin mRNA levels by 100% and GalR2-binding sites by 50%, in the rat dorsal raphe nucleus, where galanin coexists with serotonin. Furthermore, a galanin receptor antagonist, M40, attenuated the antidepressant-like effect of FLX in the forced swim test, a rodent preclinical screen commonly used to evaluate antidepressant-like efficacy. Direct activation of galanin receptors by a galanin receptor agonist, galnon, was found to produce an antidepressant-like effect in the same task. Two other antidepressant treatments also affected the galaninergic system in the monoaminergic nuclei: Electroconvulsive shock elevated galanin mRNA levels in dorsal raphe nucleus, whereas sleep deprivation increased galanin mRNA levels in the locus coeruleus, further underlining the connection between activation of the galaninergic system and antidepressant action of various clinically proven treatments.
Xiaoying Lu; Alasdair M Barr; Jefferson W Kinney; Pietro Sanna; Bruno Conti; M Margarita Behrens; Tamas Bartfai
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2005-01-12
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  102     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2005-01-19     Completed Date:  2005-03-15     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  874-9     Citation Subset:  IM    
Department of Neuropharmacology and The Harold L. Dorris Neurological Research Center, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
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MeSH Terms
Antidepressive Agents / pharmacology
Binding Sites
Fluoxetine / pharmacology*
Galanin / drug effects,  genetics,  physiology*
RNA, Messenger / drug effects
Raphe Nuclei / metabolism*
Rats, Sprague-Dawley
Receptor, Galanin, Type 2 / metabolism
Serotonin Uptake Inhibitors / pharmacology
Sleep Deprivation
Up-Regulation / drug effects
Grant Support
R01 MH63080-02/MH/NIMH NIH HHS
Reg. No./Substance:
0/Antidepressive Agents; 0/RNA, Messenger; 0/Receptor, Galanin, Type 2; 0/Serotonin Uptake Inhibitors; 54910-89-3/Fluoxetine; 88813-36-9/Galanin

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