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Oroxylin A improves attention deficit hyperactivity disorder-like behaviors in the spontaneously hypertensive rat and inhibits reuptake of dopamine in vitro
- Yoon, Seo Young, dela Peña, Ike, Kim, Sung Mok, Woo, Tae Sun, Shin, Chan Young, Son, Kun Ho, Park, Haeil, Lee, Yong Soo, Ryu, Jong Hoon, Jin, Mingli, Kim, Kyeong-Man, Cheong, Jae Hoon
- Archives of pharmacal research 2013 v.36 no.1 pp. 134-140
- agonists, antagonists, dopamine, drinking water, gamma-aminobutyric acid, haloperidol, in vitro studies, models, norepinephrine, rats
- 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.