title: Effects of atomoxetine on attention and impulsivity in the five-choice serial reaction time task in rats with lesions of dorsal noradrenergic ascending bundle.
abstract: Atomoxetine, a noradrenaline reuptake inhibitor (NRI), which is a non-stimulating medicine that is used for the treatment of patients with attention deficit hyperactivity disorder (ADHD), has been found to be effective in reducing behavioral impulsivity in rodents, but its efficacy in a dorsal noradrenergic ascending bundle (DNAB)-lesioned condition has not been examined. The present study aimed to investigate the effects of DNAB lesions on attention and impulsive control in the five-choice serial reaction time task (5-CSRTT) in rats treated with atomoxetine. The drug-induced changes in noradrenaline efflux in the medial prefrontal cortex were also measured. 5-CSRTT-trained rats were included in one of the following groups: N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4)/Atomoxetine, Sham/Atomoxetine, DSP-4/Saline, or Sham/Saline. Acute atomoxetine (0.3 mg/kg) was administered 14 days after the DSP-4 regime. The behavioral testing included manipulations of the inter-trial interval (ITI), stimulation duration and food satiety. In vivo microdialysis of the noradrenaline efflux in the medial prefrontal cortex and the expression of the noradrenaline transporter (NAT) in the DNAB areas were examined. Atomoxetine reduced impulsivity and perseveration in the long-ITI condition with no effects on any other variables. This phenomenon was not influenced by DSP-4 pre-treatment. The DNAB-lesioned rats had lower noradrenaline efflux in the medial prefrontal cortex. DSP-4 caused no change in NAT expression in the DNAB areas. These findings suggested that noradrenaline reuptake may not be exclusively responsible for the atomoxetine effects in adjusting impulsivity. The role of DNAB should also be considered, particularly in conditions requiring greater behavioral inhibition.
authors.affiliation: Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan, ROC; Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan, ROC. Electronic address: yiaping@ms75.hinet.net.
authors.forename: Yia-Ping
authors.initials: YP
authors.lastname: Liu
authors.affiliation: Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Teng-Shun
authors.initials: TS
authors.lastname: Huang
authors.affiliation: Division of Medical Research & Education, Cheng Hsin General Hospital, Taipei, Taiwan, ROC.
authors.forename: Che-Se
authors.initials: CS
authors.lastname: Tung
authors.affiliation: Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Chen-Cheng
authors.initials: CC
authors.lastname: Lin
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000344:Afferent Pathways / Q000293:injuries / Q000473:pathology; D000818:Animals; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000209:etiology; D001596:Benzylamines / Q000633:toxicity; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D002755:Choice Behavior / Q000187:drug effects; D007175:Impulsive Behavior / Q000187:drug effects*; D008297:Male; D017551:Microdialysis; D009271:Naltrexone / Q000031:analogs & derivatives / Q000633:toxicity; D009638:Norepinephrine / Q000031:analogs & derivatives* / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D011437:Propylamines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects*; D015031:Zimeldine / Q000494:pharmacology
chemical_list: D018663:Adrenergic Agents; D018759:Adrenergic Uptake Inhibitors; D001596:Benzylamines; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011437:Propylamines; D015031:Zimeldine; C002748:noradrenalone; D000069445:Atomoxetine Hydrochloride; D009271:Naltrexone; C017120:chlornaltrexamine; C012102:DSP 4; D009638:Norepinephrine
keywords: Atomoxetine; Dorsal noradrenergic ascending bundle; Five-choice serial reaction time task; Impulsivity; Microdialysis