Oroxylin A improves attention deficit hyperactivity disorder-like behaviors in the spontaneously hypertensive rat and inhibits reuptake of dopamine in vitro.
In previous studies we have demonstrated that the γ-aminobutryic acid-A (GABA-A) receptor antagonist oroxylin A has an awakening effect and it also represses ADHD-like behaviors (hyperactivity, impulsivity and inattention) in the spontaneously hypertensive rat (SHR) model of attention-deficit hyperactivity disorder (ADHD). We hypothesized that the effects of oroxylin A were exerted via the GABA-A receptor given the important role of the GABAergic system in ADHD. However, it is possible that aside from the GABAergic system, oroxylin A may influence other systems especially those implicated in ADHD (e.g. DAergic, etc.). To test this hypothesis, we evaluated the effects of GABA agonist, or dopamine (DA) antagonist in oroxylin A-induced alleviation of ADHD-like behaviors in SHR. SHR showed inattention and impulsivity as measured by the Y-maze and the electro-foot shock aversive water drinking tests, respectively. Oroxylin A significantly improved these behaviors, furthermore, its effect on SHR impulsivity was attenuated by haloperidol, a DA antagonist, but not by baicalein, an agonist of the GABA-A receptor. In vitro studies showed that oroxylin A inhibited DA uptake similar to methylphenidate, a dopamine transporter blocker, but did not influence norepinephrine uptake unlike atomoxetine, a selective NE reuptake inhibitor. Collectively, the present findings suggest that oroxylin A improves ADHD-like behaviors in SHR via enhancement of DA neurotransmission and not modulation of GABA pathway as previously reported. Importantly, the present study indicates the potential therapeutic value of oroxylin A in the treatment of ADHD.
Uimyung Research Institute for Neuroscience, Sahmyook University, Seoul 139-742, South Korea.
Seo Young
SY
Yoon
Ike
I
dela Peña
Sung Mok
SM
Kim
Tae Sun
TS
Woo
Chan Young
CY
Shin
Kun Ho
KH
Son
Haeil
H
Park
Yong Soo
YS
Lee
Jong Hoon
JH
Ryu
Mingli
M
Jin
Kyeong-Man
KM
Kim
Jae Hoon
JH
Cheong
D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D058787:GABA-A Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D005419:Flavonoids; D058787:GABA-A Receptor Antagonists; C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one; D004298:Dopamine