Thujone inhibits the function of 7-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 7 subunit of the human nicotinic acetylcholine (7 nACh) receptor expressed in Xenopus oocytes using the two-electrode voltage-clamp technique. Thujone reversibly inhibited ACh (100 M)-induced currents with an IC50 value of 24.7 M. 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] -bungarotoxin was not altered by thujone. Further experiments in SH-EP1 cells expressing human 7 nACh 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 (1.25 mg/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 7-nACh receptor and impairs cellular and behavioral correlates of cholinergic modulation of learning and memory.