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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hiraide, Sachiko Ueno, Ken-Ichi Yamaguchi, Taku Matsumoto, Machiko Yanagawa, Yoshiki Yoshioka, Mitsuhiro Togashi, Hiroko |
| Description | Country affiliation: Japan Author Affiliation: Hiraide S ( Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences, University of Hokkaido, Ishikari-Tobetsu 061-0293, Japan.) |
| 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. |
| File Format | HTM / HTML |
| ISSN | 00913057 |
| Volume Number | 105 |
| e-ISSN | 18735177 |
| Journal | Pharmacology Biochemistry and Behavior |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2013-04-01 |
| Publisher Place | United States |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Behavioral Sciences Discipline Biochemistry Discipline Pharmacology Attention Deficit Disorder With Hyperactivity Drug Therapy Behavior, Animal Drug Effects Biogenic Monoamines Metabolism Desipramine Therapeutic Use Disease Models, Animal Dopamine Uptake Inhibitors Piperazines Animals Physiopathology Pharmacology Locomotion Male Maze Learning Rats Rats, Inbred Shr Journal Article |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biological Psychiatry Behavioral Neuroscience Biochemistry Clinical Biochemistry Toxicology Pharmacology |
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