Maternal exposure to atomoxetine alters gene expression in the fetal brain.

Objective: The efficacy and safety of atomoxetine, the only licensed non-stimulant pharmacological treatment option for ADHD in Europe, is well investigated in clinical trials, the long-term effects in the developing brain still remain elusive. In vitro studies prove that besides the well-known inhibition of the norepinephrine transporter (NET) atomoxetine acts as a blocker of the N-methyl-D-aspartate (NMDA) receptor. Here we present an in vivo study carried out to investigate atomoxetine’s effect in the maturing rat brain. Methods: Pregnant Crl:SD(CD) rats were treated with atomoxetine (3 mg/kg, i.p.) and sodium chloride (0.9%, i.p.), for the period equivalent to human second to third trimenon of pregnancy. After the end of treatment hippocampus, prefrontal cortex, mesencephalon and striatum from embryos and dams were isolated for analysis of gene expression. Results: Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed altered expression of genes of the monoaminergic and glutamatergic system in both embryos and dams. Discussion: This study gives hints that atomoxetine might alter transcriptional regulation of genes of the monoaminergic and glutamatergic system in an age-dependent manner. Conclusion: Atomoxetine alters gene expression in vivo. [ABSTRACT FROM AUTHOR]