Atomoxetine blocks motor hyperactivity in neonatal 6-hydroxydopamine-lesioned rats: implications for treatment of attention-deficit hyperactivity disorder.
We recently reported that selective inhibitors of neuronal transport of norepinephrine (NE), desipramine and nisoxetine, reversed motor hyperactivity in an animal model of attention-deficit hyperactivity disorder (ADHD). In this study, we examined behavioural effects of atomoxetine, a potent new NE reuptake blocker, in juvenile male rats with neonatal 6-hydroxydopamine (6-OHDA) lesions of dopamine projections to the forebrain. 6-OHDA (100 microg) was administered intracisternally on postnatal day (PD) 5 following desipramine (25 mg/kg s.c.) pretreatment to protect noradrenergic neurons. Atomoxetine (1 mg/kg) was given intraperitoneally before recording motor activity for 90 min at PD 23-26 in a novel environment. Atomoxetine greatly reduced motor hyperactivity in 6-OHDA-lesioned rats while exhibiting transient sedative effects in sham controls. The observed effects in this animal model for ADHD are consistent with the emerging clinical use of atomoxetine as a novel, non-stimulant treatment for ADHD.
Moran-Gates
Taylor
T
Mailman Research Center, McLean Division of Massachusetts General Hospital, Belmont, 02478, USA.
Zhang
Kehong
K
Baldessarini
Ross J
RJ
Tarazi
Frank I
FI
D018663:Adrenergic Agents / Q000633:toxicity*; D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced* / Q000150:complications; D004195:Disease Models, Animal; D006948:Hyperkinesis / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D016627:Oxidopamine / Q000633:toxicity*; D011437:Propylamines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018663:Adrenergic Agents; D018759:Adrenergic Uptake Inhibitors; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride; D016627:Oxidopamine