Neuropharmacology Lab

Prof. Lih-Chu Chiou is a neuropharmacologist who graduated from National Taiwan University and was trained as an electrophysiologist in brain slice recordings at the University of Texas Medical Branch, Galveston, USA. In the early years, she employed electrophysiological approaches in the midbrain periaqueductal gray (PAG) slices to characterize the pharmacological properties of several ligands of nociception receptors, the fourth opioid receptor member. Her team has also revealed neuroplasticity changes in the PAG of animals with neuropathic pain. Later, they found orexins can induce analgesia via orexin 1 receptor-mediated endocannabinoid (eCB) synthesis in the PAG. Importantly, they found this orexin-initiated eCB signaling in the PAG can contribute to the phenomenon of stress-induced analgesia and, surprisingly, also to acupuncture-induced analgesia via median nerve stimulation. Interestingly, this signaling also exists in the ventral tegmental area and contributes to stress-induced extinguished cocaine seeking. Since 2019, Dr. Chiou has launched a drug development project initiated by a clinical case of intractable motor tics, which was sensitive to a local herb. From this herb, they have identified a flavonoid, hispidulin, as an active constituent that acted as a positive allosteric modulator (PAM) of the α6 subunit-containing GABAA receptors (α6GABAARs) in the cerebellum. Thereafter, they found several pyrazoloquinolinone (PQ) compounds synthesized by James Cook’s lab in University of Milwaukee have been identified to be the first α6GABAAR-selective PAMs by Werner Sieghart’s team at the Medical University of Vienna, and these PQ compounds can reproduce the therapeutic effects of hispidulin in animal models mimicking tic disorders and schizophrenia. Later, they further revealed that α6GABAAR-selective PAMs are effective in animal models mimicking migraine, orofacial pain, and essential tremor. Currently, they are exploring more therapeutic potentials of α6GABAAR-selective PAMs in treating neuropsychiatric disorders with unmet medical needs.