title: Effects of atomoxetine on levels of monoamines and related substances in discrete brain regions in mice intermittently deprived of rapid eye movement sleep.
abstract: An imbalance between noradrenergic and dopaminergic systems is implicated in hyperactivity disorders, such as attention deficit/hyperactivity disorder (ADHD). We previously showed that the explosive jumping behavior elicited by intermittent rapid eye movement sleep deprivation (REMSD) may serve as a useful model of ADHD (see [Biogenic Amines, 20, 99-111]). Here, we investigated whether intermittent REMSD might cause changes in monoamine turnover in the mouse forebrain. Our main findings were as follows. Intermittent REMSD led to a significant decrease in dopamine turnover and a significant increase in noradrenaline turnover in the frontal cortex. The latter effect, but not the former, was attenuated by atomoxetine, which is used clinically to treat ADHD symptoms. These results suggest (a) that intermittent REMSD induces hypernoradrenergic and hypodopaminergic states within the frontal cortex, and (b) that the therapeutic effects of atomoxetine may include an inhibition of this hypernoradrenergic state.
authors.affiliation: Department of Pharmacology, Tohoku Pharmaceutical University, Japan. niijima@tohoku-pharm.ac.jp
authors.forename: Fukie
authors.initials: F
authors.lastname: Niijima
authors.forename: Hiroko
authors.initials: H
authors.lastname: Saito
authors.forename: Shigeo
authors.initials: S
authors.lastname: Murai
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Arai
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakagawasai
authors.forename: Koichi
authors.initials: K
authors.lastname: Tan-No
authors.forename: Hiromi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Hajime
authors.initials: H
authors.lastname: Hiraga
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tadano
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D006948:Hyperkinesis / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009068:Movement; D009638:Norepinephrine / Q000378:metabolism*; D011437:Propylamines / Q000494:pharmacology* / Q000627:therapeutic use; D012892:Sleep Deprivation / Q000150:complications* / Q000378:metabolism; D012895:Sleep, REM / Q000502:physiology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride; D004298:Dopamine; D009638:Norepinephrine