Selective serotonin reuptake inhibitors (SSRIs) are important drugs in the treatment of child and adolescent psychiatric disorders. SSRIs achieve their therapeutic effect by increasing the extracellular level of 5-HT. Animal experiments indicate that supra-physiological 5-HT levels during brain development can lead to irreversible cytoarchitectural and behavioral abnormalities. Our data also indicate that postnatal administration of fluoxetine in mice results in permanent brain abnormalities including neuronal hyperexcitability in a sensory pathway and audiogenic seizures. There have been no longitudinal studies to assess the long-term effects of SSRI-administration in adults who received treatment during childhood. Such studies require many years and even decades. Developmental processes are much faster in rodents allowing the evaluation of postnatal SSRI-treatment on adult behavior in a relatively short time scale. The goals of this proposal are to better characterize the long-term adverse effects associated with the postnatal administration of SSRI in clinically relevant doses and to specify some of the mechanisms that underlie these effects. ? ?
| Oh, Ji-eun; Zupan, Bojana; Gross, Steven et al. (2009) Paradoxical anxiogenic response of juvenile mice to fluoxetine. Neuropsychopharmacology 34:2197-207 |
