Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-12-10
pubmed:abstractText
Tryptophan hydroxylase-2 (TPH2), the rate-limiting enzyme in 5-HT synthesis in the brain, is a candidate for participation in a mechanism mediating the antidepressant effect of selective 5-HT reuptake inhibitors such as fluoxetine. Using real-time reverse transcription-polymerase chain reaction (RT-PCR) and semi-quantitative RT-PCR techniques, we have examined the effects of fluoxetine administration with drinking water (7.5 mg/kg/day) for 2, 4 and 8 weeks on TPH2 mRNA expression in the midbrain part of the dorsal raphe nucleus (DRN) and in the brainstem containing the rest of the raphe complex. Fluoxetine treatment for 4 and 8 weeks significantly increased basal TPH2 mRNA levels in the midbrain, an effect that was correlated with the appearance of antidepressant-like effects in the forced swim test. A significant induction of TPH2 and 5-HT transporter (5-HTT) mRNAs was detected in the midbrain of untreated rats 24 h after the swim test. In these animals, the swim test also produced a marked decrease in 5-HT metabolite (5-hydroxyindoleacetic acid (5-HIAA)) content in the amygdala. Fluoxetine treatment for 4 and 8, but not for 2 weeks, abolished these swim-induced changes in TPH2 and 5-HTT mRNAs levels in the midbrain and 5-HIAA content in the amygdala. The results of the present study suggest that TPH2 gene expression in the midbrain part of the DRN is implicated in depression and stress response, as well as in the antidepressant fluoxetine action.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
150
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
404-12
pubmed:meshHeading
pubmed-meshheading:17950541-Animals, pubmed-meshheading:17950541-Antidepressive Agents, Second-Generation, pubmed-meshheading:17950541-Brain, pubmed-meshheading:17950541-Depressive Disorder, pubmed-meshheading:17950541-Drug Administration Schedule, pubmed-meshheading:17950541-Fluoxetine, pubmed-meshheading:17950541-Gene Expression Regulation, Enzymologic, pubmed-meshheading:17950541-Hydroxyindoleacetic Acid, pubmed-meshheading:17950541-Male, pubmed-meshheading:17950541-RNA, Messenger, pubmed-meshheading:17950541-Raphe Nuclei, pubmed-meshheading:17950541-Rats, pubmed-meshheading:17950541-Rats, Wistar, pubmed-meshheading:17950541-Serotonin, pubmed-meshheading:17950541-Serotonin Plasma Membrane Transport Proteins, pubmed-meshheading:17950541-Serotonin Uptake Inhibitors, pubmed-meshheading:17950541-Stress, Psychological, pubmed-meshheading:17950541-Tryptophan Hydroxylase, pubmed-meshheading:17950541-Up-Regulation
pubmed:year
2007
pubmed:articleTitle
Up-regulation of tryptophan hydroxylase-2 mRNA in the rat brain by chronic fluoxetine treatment correlates with its antidepressant effect.
pubmed:affiliation
Functional Neurogenomics Laboratory, Institute of Cytology and Genetics, Russian Academy of Science, Novosibirsk 630090, Russia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't