Thujone inhibits the function of α₇-nicotinic acetylcholine receptors and impairs nicotine-induced memory enhancement in one-trial passive avoidance paradigm

Effects of thujone, a major ingredient of absinthe, wormwood oil and some herbal medicines, were tested on the function of α₇ subunit of the human nicotinic acetylcholine (α₇ nACh) receptor expressed in Xenopus oocytes using the two-electrode voltage-clamp technique. Thujone reversibly inhibited ACh (100 μM)-induced currents with an IC₅₀ value of 24.7 μM. 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 α₇ 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 α7-nACh receptor and impairs cellular and behavioral correlates of cholinergic modulation of learning and memory.