Effect of the attention deficit/hyperactivity disorder drug atomoxetine on extracellular concentrations of norepinephrine and dopamine in several brain regions of the rat.
Atomoxetine is a selective inhibitor of norepinephrine transporters and is currently being used in the pharmacotherapy of attention deficit/hyperactivity disorder (ADHD). We have previously shown that atomoxetine increased extracellular (EX) concentrations of norepinephrine and dopamine in prefrontal cortex, but unlike the psychostimulant methylphenidate, did not alter dopamine(EX) in nucleus accumbens or striatum. Using the in vivo microdialysis technique in rat, we investigated the effects of atomoxetine on norepinephrine(EX) and dopamine(EX) concentrations in several other brain regions and also evaluated the role of inhibitory autoreceptors on atomoxetine-induced increases of norepinephrine(EX) concentrations. Atomoxetine (3mg/kg i.p.) increased norepinephrine(EX) robustly in prefrontal cortex, occipital cortex, lateral hypothalamus, dorsal hippocampus and cerebellum, suggesting that norepinephrine(EX) is increased throughout the brain by atomoxetine. In lateral hypothalamus and occipital cortex where dopamine(EX) was quantifiable, atomoxetine did not increase dopamine(EX) concentrations, in contrast to parallel increases of norepinephrine(EX) and dopamine(EX) in prefrontal cortex, indicating a unique effect in prefrontal cortex. Administration of the alpha(2)-adrenergic antagonist idazoxan 1h after atomoxetine resulted in increases in prefrontal cortical norepinephrine efflux greater than either compound alone, indicating an attenuating effect of the adrenergic autoreceptors on norepinephrine efflux.
Swanson
Chad J
CJ
Lundbeck Research USA, 215 College Road, Paramus, NJ 07652-1431, USA.
Perry
Kenneth W
KW
Koch-Krueger
Susanne
S
Katner
Jason
J
Svensson
Kjell A
KA
Bymaster
Frank P
FP
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000069445:Atomoxetine Hydrochloride; D001921:Brain / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects*; D008297:Male; D017551:Microdialysis / Q000379:methods; D009638:Norepinephrine / Q000378:metabolism*; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018759:Adrenergic Uptake Inhibitors; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride; D004298:Dopamine; D009638:Norepinephrine