title: Behavioural effects of monoamine reuptake inhibitors on symptomatic domains in an animal model of attention-deficit/hyperactivity disorder.
abstract: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurobehavioural disorder. Several lines of evidence have implicated monoamine signalling systems, including transporters and receptors, in the pathogenesis of ADHD. We explored the heterogeneity of neural mechanisms that may possibly underlie symptomatic abnormalities in ADHD, by investigating the effects of monoamine reuptake inhibitors with differential spectrums for each monoamine transporter on ADHD-like behaviours in an animal model of ADHD, i.e. juvenile (6-week-old) male stroke-prone spontaneously hypertensive rats (SHRSP/Ezo). The impaired spontaneous alternation performance in a Y-maze task, demonstrated the inattentive features of SHRSP/Ezo, was improved by a selective DA reuptake inhibitor GBR-12909 (1 and 3mg/kg, i.p.). Desipramine (1, 3 and 10mg/kg, i.p.) and milnacipran (30mg/kg, i.p.), which possess a noradrenaline (NA) reuptake inhibitory activity, also ameliorated inattentive behaviour. Increased locomotor activity in open-field apparatus and total arm entries in a Y-maze task, which demonstrate the hyperactive features of SHRSP/Ezo, were improved by desipramine and milnacipran, but impaired by a high dose of GBR-12909 (10mg/kg, i.p.). A selective serotonin (5-HT) reuptake inhibitor fluvoxamine (10 and 30mg/kg, i.p.), did not affect inattention but significantly suppressed hyperactivity at a high dose (30mg/kg, i.p.). Moreover, a low dose of fluvoxamine (3mg/kg, i.p.) ameliorated the increased open arm spent time in an elevated plus-maze without affecting total arm entries, indicating an effect on impulsive features based on the anxiolytic characteristics of SHRSP/Ezo. These behavioural effects of monoamine reuptake inhibitors support the heterogeneity of monoaminergic systems, which are responsible for ADHD-like behaviours in SHRSP/Ezo. These findings may provide pharmacological evidence for the development of ADHD treatments that target more appropriate monoamine transporters.
authors: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences, University of Hokkaido, Ishikari-Tobetsu 061-0293, Japan.
authors: Sachiko
authors: S
authors: Hiraide
authors: Ken-Ichi
authors: K
authors: Ueno
authors: Taku
authors: T
authors: Yamaguchi
authors: Machiko
authors: M
authors: Matsumoto
authors: Yoshiki
authors: Y
authors: Yanagawa
authors: Mitsuhiro
authors: M
authors: Yoshioka
authors: Hiroko
authors: H
authors: Togashi
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018782:Maze Learning; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D015306:Biogenic Monoamines; D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; C043425:vanoxerine; D003891:Desipramine