Effects of atomoxetine on levels of monoamines and related substances in discrete brain regions in mice intermittently deprived of rapid eye movement sleep.
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.
Niijima
Fukie
F
Department of Pharmacology, Tohoku Pharmaceutical University, Japan. niijima@tohoku-pharm.ac.jp
Saito
Hiroko
H
Murai
Shigeo
S
Arai
Yuichiro
Y
Nakagawasai
Osamu
O
Tan-No
Koichi
K
Watanabe
Hiromi
H
Hiraga
Hajime
H
Tadano
Takeshi
T
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
D018759:Adrenergic Uptake Inhibitors; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride; D004298:Dopamine; D009638:Norepinephrine