engleski

The effect of chronic fluoxetine on anxiety- like behavior and expression of 5HT-related proteins in rats with constitutionally altered 5HT homeostasis

Background: Serotonin (5HT) is a monoamine neurotransmitter/ neuromodulator widely distributed in brain and plays an important role in variety of behaviors and behavioral disorders, including anxiety and depression. Therapeutic effects of fluoxetine, one of widely prescribed psychotropic drugs, include inhibition of serotonin transporter (5HTT) and desensitization of 5HT1A receptors which leads to the enhancement of 5HT transmission. The patient’s ability to response to fluoxetine (and other SSRIs) treatment is greatly variable and genetic variants of the 5HTT, which are believed to influence serotonergic neurotransmission, might influence interindividual variability in pharamacotherapeutic response. In our serotonin research we use Wistar-Zagreb 5HT rats, an animal model with constitutionally high or low 5HTT activity (termed high- and low-5HT subline), developed by selective breeding toward extremes of this parameter in our laboratory. In addition to differential regulation of peripheral serotonin, 5HT- sublines displayed also constitutional alteration in brain 5HT homeostasis. Thus we have demonstrate previously that animals from the high-5HT subline exhibit increased anxiety- like behavior, but no measurable differences in baseline functionality or expression of 5HT1A receptors between sublines were found. Here, we examined the response of 5HT-sublines to the chronic administration of fluoxetine. Methods: We treated male rats from high- and low 5HT- sublines with fluoxetine (6 mg/kg i.p) for 27 days. Anxiety-like behavior was evaluated 24h after 23th injection by use of elevated-plus maze paradigm. The expression of 5HTT and 5HT1A receptor was assessed in frontal cortices, 48h after the last injection, by use of RT-PCR. At the same time point we measured also cortical 5HT levels using ELISA assay. Results: Fluoxetine-induced reduction of anxiety-like behavior, measured as increased time spent in open arms, was observed in high-5HT animals only. Further, chronic fluoxetine increased the expression of 5HTT in high-5HT animals and decreased it in animals from the low-5HT subline. The expression of cortical 5HT1A receptors was not affected in high-5HT animals, while in the low 5HT-subline reduction in expression was noted. Tissue level of serotonin in fluoxetine-treated animals was significantly higher in high-5HTsubline as compared to low- 5HT subline.

anxiety; animal model; fluoxetine; gene expression; serotonin; Wistar-Zagreb 5HT rats

http://www.biomedcentral.com/content/pdf/2050- 6511-13-S1-A30.pdf