Effects of Atomoxetine on Motor and Cognitive Behaviors and Brain Electrophysiological Activity of Dopamine Transporter Knockout Rats

Abstract

Changes in dopaminergic and noradrenergic transmission are considered to be the underlying cause of attention deficit and hyperactivity disorder (ADHD). Atomoxetine (ATX) is a selective norepinephrine transporter (NET) inhibitor that is currently used for ADHD treatment. In this study, we aimed to evaluate the effect of atomoxetine on the behavior and brain activity of dopamine transporter knockout (DAT-KO) rats, which are characterized by an ADHD-like behavioral phenotype. Prepulse inhibition (PPI) was assessed in DAT-KO and wild type rats after saline and ATX injections, as well as behavioral parameters in the Hebb–Williams maze and power spectra and coherence of electrophysiological activity. DAT-KO rats demonstrated a pronounced behavioral and electrophysiological phenotype, characterized by hyperactivity, increased number of errors in the maze, repetitive behaviors and disrupted PPI, changes in cortical and striatal power spectra and interareal coherence. Atomoxetine significantly improved PPI and decreased repetitive behaviors in DAT-KO rats and influenced behavior of wild-type rats. ATX also led to significant changes in power spectra and coherence of DAT-KO and wild type rats. Assessment of noradrenergic modulation effects in DAT-KO provides insight into the intricate interplay of monoaminergic systems, although further research is still required to fully understand the complexity of this interaction.

A Custom Solution for Acoustic Startle Response Setup with Spike2-Based Data Acquisition Interface

“…The presented software for CED interface offers an affordable and straightforward approach for performing experiments on PPI of acoustic startle response. Similar to earlier articles [ 9 , 10 ], this study showed high effectiveness and valid output results.…”

“…According to the results of experiments in mice (males and females), DAT-KO animals demonstrated a reduced prepulse inhibition compared to WT mice [ 8 , 17 ]. According to the results of our previous experiments in male DAT knockout rats [ 9 , 10 ], ASR in response to single pulses was generally higher than to prepulse+pulse pairs, and PPI in male DAT-KO rats was significantly lower than in male WT rats. The data obtained in female WT and DAT-KO rats show the same tendency; ASR to single pulses is higher than ASR to prepulse+pulse pairs, and PPI in female DAT-KO rats is reduced compared to that in female WT.…”

“…PPI is commonly performed in animal models of human disease to investigate mechanisms of impairment and drug testing. [ 4 , 8 , 9 , 10 ]. Various types of startle stimuli are applied, including acoustic, visual, and tactile [ 3 , 4 ].…”

“…The software has been successfully used in our previous studies, and the results have been published earlier [ 9 , 10 ]. The current paper provides an example of using Spike2-based data acquisition interface to assess PPI in wild-type and knockout rats.…”

Pre-Pulse Inhibition of an escape response in adult fruit fly, Drosophila melanogaster

“…We hope that our work can contribute to finding solutions for the treatment of such debilitating mental disorders as Schizophrenia 79 and Bipolar Disorder 80 . It further may contribute to develop treatment for Neurodevelopmental disorders including Autistic Spectrum Disorder 81 , Attention Deficit Hyperactivity Disorder (ADHD) 82 , and monogenic conditions such as Fragile-X syndrome 83 , all known to affect PPI performance in human patients.…”