Oroxylin A improves attention deficit hyperactivity disorder-like behaviors in the spontaneously hypertensive rat and inhibits reuptake of dopamine in vitro

Arch Pharm Res. 2013 Jan;36(1):134-40. doi: 10.1007/s12272-013-0009-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Attention Deficit Disorder with Hyperactivity / drug therapy*
  • Attention Deficit Disorder with Hyperactivity / metabolism
  • Attention Deficit Disorder with Hyperactivity / psychology
  • Behavior, Animal / drug effects*
  • Disease Models, Animal
  • Dopamine / metabolism*
  • Dopamine Agonists / pharmacology
  • Dopamine Plasma Membrane Transport Proteins / antagonists & inhibitors*
  • Flavonoids / administration & dosage
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use*
  • GABA-A Receptor Antagonists / administration & dosage
  • GABA-A Receptor Antagonists / pharmacology
  • GABA-A Receptor Antagonists / therapeutic use*
  • HEK293 Cells
  • Humans
  • Male
  • Maze Learning / drug effects
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY


  • Dopamine Agonists
  • Dopamine Plasma Membrane Transport Proteins
  • Flavonoids
  • GABA-A Receptor Antagonists
  • 5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one
  • Dopamine