Rearing in an Enriched Environment Ameliorates the ADHD-like Behaviors of Lister Hooded Rats While Suppressing Neuronal Activities in the Medial Prefrontal Cortex
Ryo Utsunomiya,
Kanta Mikami,
Tomomi Doi,
Mohammed E. Choudhury,
Toshihiro Jogamoto,
Naohito Tokunaga,
Eiichi Ishii,
Mariko Eguchi,
Hajime Yano,
Junya Tanaka
Affiliations
Ryo Utsunomiya
Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon 791-0295, Japan
Kanta Mikami
Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon 791-0295, Japan
Tomomi Doi
Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon 791-0295, Japan
Mohammed E. Choudhury
Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon 791-0295, Japan
Toshihiro Jogamoto
Department of Pediatrics, Graduate School of Medicine, Ehime University, Toon 791-0295, Japan
Naohito Tokunaga
Division of Medical Research Support, the Advanced Research Support Center (ADRES), Ehime University, Toon 791-0295, Japan
Eiichi Ishii
Department of Pediatrics, Imabari City Medical Association General Hospital, Imabari 794-0026, Japan
Mariko Eguchi
Department of Pediatrics, Graduate School of Medicine, Ehime University, Toon 791-0295, Japan
Hajime Yano
Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon 791-0295, Japan
Junya Tanaka
Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon 791-0295, Japan
In addition to genetic factors, environmental factors play a role in the pathogenesis of attention deficit/hyperactivity disorder (ADHD). This study used Lister hooded rats (LHRs) as ADHD model animals to evaluate the effects of environmental factors. Male LHR pups were kept in four rearing conditions from postnatal day 23 (4 rats in a standard cage; 12 rats in a large flat cage; and 4 or 12 rats in an enriched environment [EE]) until 9 weeks of age. EE rearing but not rearing in a large flat cage decreased the activity of LHRs in the open field test that was conducted for 7 consecutive days. In the drop test, most rats reared in an EE remained on a disk at a height, whereas most rats reared in a standard cage fell off. RNA sequencing revealed that the immediate-early gene expression in the medial prefrontal cortex of LHRs reared in an EE was reduced. cFos-expressing neurons were reduced in number in LHRs reared in an EE. These results suggest that growing in an EE improves ADHD-like behaviors and that said improvement is due to the suppression of neuronal activity in the mPFC.