title: ABT-724 alleviated hyperactivity and spatial learning impairment in the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder.
abstract: Dysfunction of dopamine D4 receptor (D4R) is linked to attention-deficit/hyperactivity disorder (ADHD) as well as ADHD associated cognitive impairment. Here, we tested the possible therapeutic benefit of the D4R-selective agonist ABT-724 in adolescent spontaneously hypertensive rats (SHRs). ABT-724-treated SHRs were administered ABT-724 (0.04mg/kg, 0.16mg/kg or 0.64mg/kg) from postnatal day (P) 28 to P32. Control SHRs and Sprague-Dawley (SD) rats were injected with saline. Then two cohorts of rats were tested in the open field and Làt maze that measured locomotion and non-selective attention (NSA), respectively. Another cohort of rats was subjected to water maze task for evaluation of spatial learning and memory. We found that control SHRs displayed hyperactivity as well as impaired NSA and spatial learning compared with normotensive SD rats. ABT-724 (0.16 and 0.64mg/kg) treatment alleviated hyperactivity and spatial learning impairment in SHRs. No dose of ABT-724 tested altered NSA in SHRs. Our results raise the possibility that ABT-724 may be used as a therapeutic intervention for ADHD patients during adolescence.
authors.affiliation: Pediatric Department of Qilu Hospital, Shandong University, Jinan, China; Brain Science Research Institute, Shandong University, Jinan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yin
authors.affiliation: Pediatric Department of Qilu Hospital, Shandong University, Jinan, China; Brain Science Research Institute, Shandong University, Jinan, China.
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Cao
authors.affiliation: Women's Hospital School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yu
authors.affiliation: Pediatric Department of Qilu Hospital, Shandong University, Jinan, China; Brain Science Research Institute, Shandong University, Jinan, China.
authors.forename: Liang-Jing
authors.initials: LJ
authors.lastname: Guo
authors.affiliation: Pediatric Department of Qilu Hospital, Shandong University, Jinan, China; Brain Science Research Institute, Shandong University, Jinan, China.
authors.forename: Ruo-Peng
authors.initials: RP
authors.lastname: Sun
authors.affiliation: Pediatric Department of Qilu Hospital, Shandong University, Jinan, China; Brain Science Research Institute, Shandong University, Jinan, China. Electronic address: leigefei@sdu.edu.cn.
authors.forename: Ge-Fei
authors.initials: GF
authors.lastname: Lei
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000523:psychology; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D050638:Receptors, Dopamine D4 / Q000819:agonists*; D065853:Spatial Learning / Q000187:drug effects*
chemical_list: C487766:ABT724; D001562:Benzimidazoles; D010879:Piperazines; D011725:Pyridines; D050638:Receptors, Dopamine D4
keywords: Attention-deficit/hyperactivity disorder; Làt maze; Morris water maze; Open field