title: Chronic fluoxetine treatment affects gene expression of catecholamine enzymes in the heart of depression model rats.
abstract: Depression is associated with increased risk of coronary heart diseases. Selective serotonin reuptake inhibitors (SSRIs) have been proved to be very effective in normalizing symptoms of depression, but the data on possible influence of these drugs on cardiovascular function is controversial. Applying Taqman RT-PCR assay, the effect of chronic treatment with a SSRI antidepressant fluoxetine has been investigated on gene expression of catecholamine biosynthetic enzymes in all four heart chambers of rats with signs of depression. Depression was induced by exposing the animals to chronic unpredictable mild stress (CUMS). Tyrosine-hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) mRNA levels were decreased both in right and left atria, while phenylethanolamine N-methyltransferase (PNMT) mRNAs were increased in left atria and both ventricles of depression model rats. Fluoxetine elevated gene expression of TH and DBH in atria, but did not influence this process in the ventricles. Also, this antidepressant did not express a significant effect on the level of PNMT mRNA both in atria and ventricles. These results indicate that fluoxetine acted stimulating noradrenaline synthesis in the heart, which could lead to increased risk of heart disease.
authors.affiliation: Laboratory for Molecular Biology and Endocrinology, Institute of Nuclear Sciences "Vinca", University of Belgrade, 11 000 Belgrade, Serbia. snatally@vinca.rs
authors.forename: Natasa
authors.initials: N
authors.lastname: Spasojevic
authors.forename: Predrag
authors.initials: P
authors.lastname: Jovanovic
authors.forename: Sladjana
authors.initials: S
authors.lastname: Dronjak
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000096:biosynthesis; D003863:Depression / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D004195:Disease Models, Animal; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D005473:Fluoxetine / Q000009:adverse effects* / Q000627:therapeutic use; D015870:Gene Expression / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects / Q000201:enzymology; D006352:Heart Ventricles / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010625:Phenylethanolamine N-Methyltransferase / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D013315:Stress, Psychological / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
chemical_list: D002395:Catecholamines; D004299:Dopamine beta-Hydroxylase; D005473:Fluoxetine; D010625:Phenylethanolamine N-Methyltransferase; D017367:Selective Serotonin Reuptake Inhibitors; D014446:Tyrosine 3-Monooxygenase