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Expression of 22 serotonin-related genes in rat brain after subacute serotonin depletion or reuptake inhibition

Journal article
Authors Jakob Näslund
Erik Studer
Staffan Nilsson
Elias Eriksson
Published in Acta Neuropsychiatrica
Volume 32
Issue 3
Pages 159-165
ISSN 09242708 (ISSN)
Publication year 2020
Published at Department of Mathematical Sciences
Institute of Neuroscience and Physiology, Department of Pharmacology
Pages 159-165
Language en
Keywords amygdala, hippocampus, prefrontal cortex, Serotonin, SSRI
Subject categories Pharmaceutical Sciences


Objective:Although the assessment of expression of serotonin-related genes in experimental animals has become a common strategy to shed light on variations in brain serotonergic function, it remains largely unknown to what extent manipulation of serotonin levels causes detectable changes in gene expression. We therefore chose to investigate how sub-acute depletion or elevation of brain serotonin influences the expression of a number of serotonin-related genes in six brain areas.Methods:Male Wistar rats were for three days administered a serotonin synthesis inhibitor, para-chlorophenylalanine (p-CPA), or a serotonin reuptake inhibitor, paroxetine, and then sacrificed. The expression of a number of serotonin-related genes in the raphe nuclei, hypothalamus, amygdala, striatum, hippocampus and prefrontal cortex were investigated using rt-qPCR.Results:While most of the studied genes were uninfluenced by paroxetine treatment, we could observe a robust down-regulation of tryptophan hydroxylase-2 in the brain region where the serotonergic cell bodies reside, i.e. the raphe nuclei. p-CPA induced a significant increase in the expression of Htr1b and Htr2a in amygdala and of Htr2c in the striatum, and a marked reduction in the expression of Htr6 in prefrontal cortex; also, it enhanced the expression of the brain-derived neurotrophic factor (Bdnf) in raphe and hippocampus.Conclusion:With some notable exceptions, the expression of most of the studied genes is left unchanged by short-term modulation of extracellular levels of serotonin. © Scandinavian College of Neuropsychopharmacology 2020.

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