title: Thujone inhibits the function of α7-nicotinic acetylcholine receptors and impairs nicotine-induced memory enhancement in one-trial passive avoidance paradigm.
abstract: Effects of thujone, a major ingredient of absinthe, wormwood oil and some herbal medicines, were tested on the function of α7subunit of the human nicotinic acetylcholine (α7nACh) receptor expressed in Xenopus oocytes using the two-electrode voltage-clamp technique. Thujone reversibly inhibited ACh (100μM)-induced currents with an IC50value of 24.7μM. The effect of thujone was not dependent on the membrane potential and did not involve Ca2+-dependent Cl-channels expressed endogenously in oocytes. Inhibition by thujone was not reversed by increasing ACh concentrations. Moreover, specific binding of [125I] α-bungarotoxin was not altered by thujone. Further experiments in SH-EP1 cells expressing human α7nACh receptor indicated that thujone suppressed choline induced Ca2+transients in a concentration-dependent manner. In rat hippocampal CA3-dentate gyrus synapses, nicotine-induced enhancement of long-term potentiation was also inhibited by thujone. Furthermore, the results observed in in-vivo one-trial passive avoidance paradigm show that thujone (1.25mg/kg, i.p.) significantly impaired nicotine-induced enhancement of learning and memory in Wistar rats. Collectively, our results indicate that thujone inhibits the function of the α7-nACh receptor and impairs cellular and behavioral correlates of cholinergic modulation of learning and memory.
authors.affiliation: Departments of Pharmacology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Sultan
authors.affiliation: Department of Biological Sciences, Schmid College of Science and Technology, Chapman University, One University Drive, Orange, CA 92866, USA.
authors.forename: Keun-Hang Susan
authors.initials: KS
authors.lastname: Yang
authors.affiliation: Departments of Pharmacology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
authors.forename: Dmitro
authors.initials: D
authors.lastname: Isaev
authors.affiliation: Departments of Pharmacology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
authors.forename: Eslam El
authors.initials: EE
authors.lastname: Nebrisi
authors.affiliation: Departments of Pharmacology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
authors.forename: Nurulain
authors.initials: N
authors.lastname: Syed
authors.affiliation: Departments of Pharmacology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
authors.forename: Nadia
authors.initials: N
authors.lastname: Khan
authors.affiliation: Department of Physiology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Howarth
authors.affiliation: Departments of Pharmacology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
authors.forename: Bassem
authors.initials: B
authors.lastname: Sadek
authors.affiliation: Departments of Pharmacology, College of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates; Department of Basic Medical Sciences, College of Medicine, Qatar University, Doha, Qatar. Electronic address: murat.oz@qu.edu.qa.
authors.forename: Murat
authors.initials: M
authors.lastname: Oz
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D000081008:Bicyclic Monoterpenes; D002118:Calcium / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects*; D039821:Monoterpenes / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D017208:Rats, Wistar; D014982:Xenopus laevis; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics / Q000502:physiology*
chemical_list: D000081008:Bicyclic Monoterpenes; D039821:Monoterpenes; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; C005790:beta-thujone; D000109:Acetylcholine; D002118:Calcium
keywords: Absinthe; Nicotinic receptors; Thujone; Xenopus oocyte; memory; passive avoidance paradigm