GABA sub(A) receptor subtype selectivity underlying selective anxiolytic effect of baicalin

• Published in: Neuropharmacology 2008-12, Vol.55 (7), p.1231-1237
• Main Authors: Wang, Feng, Xu, Zhiwen, Ren, Lihuan, Tsang, Shui Ying, Xue, Hong
• Format: Article
• Language: English
• ISSN: 0028-3908
• DOI: 10.1016/j.neuropharm.2008.07.040

Baicalin, a naturally occurring flavonoid, was previously reported to induce anxiolytic-like effect devoid of sedation and myorelaxation in mice, acting through type A gamma -aminobutyric acid (GABA sub(A)) receptor benzodiazepine (BZ) site. The present study further expanded the behavioral pharmacology profile of baicalin and subtype selectivity was explored as a possible mechanism underlying its in vivo effects on mice. Baicalin was characterized using convulsion, memory, and motor function related animal tests; and its selectivity towards recombinant GABA sub(A) receptor subtypes expressed in HEK 293T cells was determined by radioligand binding assay and electrophysiological studies. In the picrotoxin-induced seizure, step-through passive avoidance and rotarod tests, the anticonvulsant, amnesic and motor incoordination effects commonly associated with classical BZs were not observed when baicalin was administered at effective anxiolytic doses, demonstrating a separation of the anticonvulsant, amnesic and motor incoordination effects from the anxiolytic-like effect. Although baicalin exhibited higher binding affinity for the alpha sub(1)-containing GABA sub(A) subtype compared with alpha sub(2)-, alpha sub(3)-, and alpha sub(5)-containing subtypes, this was not statistically significant. In contrast to the classical BZ diazepam, baicalin showed significant preference for alpha sub(2)- and alpha sub(3)- containing subtypes compared to alpha sub(1)- and alpha sub(5)-containing subtypes in whole-cell patch clamp studies (P < 0.01). Its subtype selectivity suggested that baicalin exerted its in vivo anxiolytic-like effect mainly through the alpha sub(2)- and alpha sub(3)-containing subtypes. Therefore, the present study revealed an underlying mechanism for the selective anxiolytic profile of baicalin, suggesting alpha sub(2)- and alpha sub(3)-containing subtypes were important drug targets for flavonoid-based anxiolytics.