TY - JOUR

T1 - Effects of Atomoxetine on Motor and Cognitive Behaviors and Brain Electrophysiological Activity of Dopamine Transporter Knockout Rats

AU - Ptukha, Maria

AU - Fesenko, Zoia

AU - Belskaya, Anastasia

AU - Gromova, Arina

AU - Pelevin, Arseniy

AU - Kurzina, Natalia

AU - Gainetdinov, Raul R

AU - Volnova, Anna

N1 - Publisher Copyright: © 2022 by the authors.

PY - 2022/10/14

Y1 - 2022/10/14

N2 - 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.

AB - 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.

KW - ADHD

KW - atomoxetine

KW - coherence

KW - dopamine

KW - dopamine transporter knockout (DAT-KO) rats

KW - norepinephrine transporter (NET)

KW - power spectra

KW - prepulse inhibition

UR - http://www.scopus.com/inward/record.url?scp=85140450367&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/551a2c26-627b-3572-b471-3d37204458e1/

U2 - 10.3390/biom12101484

DO - 10.3390/biom12101484

M3 - Article

C2 - 36291693

VL - 12

JO - Biomolecules

JF - Biomolecules

SN - 2218-273X

IS - 10

M1 - 1484

ER -