TY - JOUR

T1 - A New Paradigm for Training Hyperactive Dopamine Transporter Knockout Rats: Influence of Novel Stimuli on Object Recognition

AU - Kurzina, Natalia P.

AU - Volnova, Anna B.

AU - Aristova, Irina Y.

AU - Gainetdinov, Raul R.

N1 - Publisher Copyright: © Copyright © 2021 Kurzina, Volnova, Aristova and Gainetdinov. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/4/22

Y1 - 2021/4/22

N2 - Attention deficit hyperactivity disorder (ADHD) is believed to be connected with a high level of hyperactivity caused by alterations of the control of dopaminergic transmission in the brain. The strain of hyperdopaminergic dopamine transporter knockout (DAT-KO) rats represents an optimal model for investigating ADHD-related pathological mechanisms. The goal of this work was to study the influence of the overactivated dopamine system in the brain on a motor cognitive task fulfillment. The DAT-KO rats were trained to learn an object recognition task and store it in long-term memory. We found that DAT-KO rats can learn to move an object and retrieve food from the rewarded familiar objects and not to move the non-rewarded novel objects. However, we observed that the time of task performance and the distances traveled were significantly increased in DAT-KO rats in comparison with wild-type controls. Both groups of rats explored the novel objects longer than the familiar cubes. However, unlike controls, DAT-KO rats explored novel objects significantly longer and with fewer errors, since they preferred not to move the non-rewarded novel objects. After a 3 months’ interval that followed the training period, they were able to retain the learned skills in memory and to efficiently retrieve them. The data obtained indicate that DAT-KO rats have a deficiency in learning the cognitive task, but their hyperactivity does not prevent the ability to learn a non-spatial cognitive task under the presentation of novel stimuli. The longer exploration of novel objects during training may ensure persistent learning of the task paradigm. These findings may serve as a base for developing new ADHD learning paradigms.

AB - Attention deficit hyperactivity disorder (ADHD) is believed to be connected with a high level of hyperactivity caused by alterations of the control of dopaminergic transmission in the brain. The strain of hyperdopaminergic dopamine transporter knockout (DAT-KO) rats represents an optimal model for investigating ADHD-related pathological mechanisms. The goal of this work was to study the influence of the overactivated dopamine system in the brain on a motor cognitive task fulfillment. The DAT-KO rats were trained to learn an object recognition task and store it in long-term memory. We found that DAT-KO rats can learn to move an object and retrieve food from the rewarded familiar objects and not to move the non-rewarded novel objects. However, we observed that the time of task performance and the distances traveled were significantly increased in DAT-KO rats in comparison with wild-type controls. Both groups of rats explored the novel objects longer than the familiar cubes. However, unlike controls, DAT-KO rats explored novel objects significantly longer and with fewer errors, since they preferred not to move the non-rewarded novel objects. After a 3 months’ interval that followed the training period, they were able to retain the learned skills in memory and to efficiently retrieve them. The data obtained indicate that DAT-KO rats have a deficiency in learning the cognitive task, but their hyperactivity does not prevent the ability to learn a non-spatial cognitive task under the presentation of novel stimuli. The longer exploration of novel objects during training may ensure persistent learning of the task paradigm. These findings may serve as a base for developing new ADHD learning paradigms.

KW - ADHD model

KW - dopamine transporter knockout rats

KW - long-term memory

KW - novelty

KW - recognition memory

KW - LONG-TERM-MEMORY

KW - DEFICIT

KW - SCHIZOPHRENIA

KW - MECHANISMS

KW - HIPPOCAMPUS

KW - DYSREGULATION

KW - DISORDER

KW - NOVELTY SEEKING

KW - MICE

KW - MODULATION

UR - http://www.scopus.com/inward/record.url?scp=85105400260&partnerID=8YFLogxK

U2 - 10.3389/fnbeh.2021.654469

DO - 10.3389/fnbeh.2021.654469

M3 - Article

C2 - 33967714

AN - SCOPUS:85105400260

VL - 15

SP - 654469

JO - Frontiers in Behavioral Neuroscience

JF - Frontiers in Behavioral Neuroscience

SN - 1662-5153

M1 - 654469

ER -