Metabolite profiling of antidepressant drug action reveals novel drug targets beyond monoamine elevation

Currently used antidepressants elevate monoamine levels in the synaptic cleft. There is good reason to assume that this is not the only source for antidepressant therapeutic activities and that secondary downstream effects may be relevant for alleviating symptoms of depression. We attempted to eluci...

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Bibliographic Details
Published inTranslational psychiatry Vol. 1; no. 12; p. e58
Main Authors Webhofer, C, Gormanns, P, Tolstikov, V, Zieglgänsberger, W, Sillaber, I, Holsboer, F, Turck, C W
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 13.12.2011
Nature Publishing Group
Subjects
631/80/86
692/53
692/699/476/1414
692/700/565/1436
Animals
Antidepressive Agents, Second-Generation - pharmacology
Behavior, Animal - drug effects
Behavioral Sciences
Biogenic Monoamines - antagonists & inhibitors
Biogenic Monoamines - biosynthesis
Biological Psychology
Biomarkers - metabolism
Drug Delivery Systems - methods
Gas Chromatography-Mass Spectrometry
Hippocampus - drug effects
Hippocampus - metabolism
Medicine
Medicine & Public Health
Metabolome - drug effects
Mice
Mice, Inbred DBA
Neurosciences
Original
original-article
Paroxetine - pharmacology
Pharmacotherapy
Psychiatry
novel antidepressant drug targets
paroxetine
biomarker
pathway analysis
metabolite profiling
antidepressant
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Summary:Currently used antidepressants elevate monoamine levels in the synaptic cleft. There is good reason to assume that this is not the only source for antidepressant therapeutic activities and that secondary downstream effects may be relevant for alleviating symptoms of depression. We attempted to elucidate affected biochemical pathways downstream of monoamine reuptake inhibition by interrogating metabolomic profiles in DBA/2Ola mice after chronic paroxetine treatment. Metabolomic changes were investigated using gas chromatography-mass spectrometry profiling and group differences were analyzed by univariate and multivariate statistics. Pathways affected by antidepressant treatment were related to energy metabolism, amino acid metabolism and hormone signaling. The identified pathways reveal further antidepressant therapeutic action and represent targets for drug development efforts. A comparison of the central nervous system with blood plasma metabolite alterations identified GABA, galactose-6-phosphate and leucine as biomarker candidates for assessment of antidepressant treatment effects in the periphery.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
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ISSN:2158-3188
2158-3188
DOI:10.1038/tp.2011.56