L-theanine attenuates nicotine reward and withdrawal signs in mice

Neurosci Lett. 2023 Jun 11:807:137279. doi: 10.1016/j.neulet.2023.137279. Epub 2023 Apr 25.

Abstract

Background: L-theanine, 2-amino-4-(ethylcarbamoyl) butyric acid, an amino acid detected in green tea leaves, is used as a dietary supplement to attenuate stress and enhance mood and cognition. Furthermore, L-theanine induces anxiolytic effects in humans. Recently, L-theanine was reported to reduce morphine physical dependence in primates, suggesting the potential usefulness of L-theanine for drug dependence intervention.

Objective: The aim of this study is to determine whether L-theanine attenuates nicotine-withdrawal (somatic and affective signs) and nicotine reward in mice. We also investigated the effects of L-theanine on nicotinic receptors binding and function.

Methods: ICR male mice rendered dependent to nicotine through implanted subcutaneous osmotic minipumps for 14 days undertook precipitated nicotine withdrawal by mecamylamine on day 15. Anxiety-like behaviors using LDB, somatic signs observation and hot plate latency were assessed consecutively after treatment with L-theanine. Furthermore, we examined the effect of L-theanine on acute nicotine responses and nicotine conditioned reward in mice and on expressed nicotinic receptors in oocytes.

Key findings: L-theanine reduced in a dose-dependent manner anxiety-like behavior, hyperalgesia and somatic signs during nicotine withdrawal. Also, L-theanine decreased the nicotine CPP, but it did not affect the acute responses of nicotine. Finally, L-theanine did not alter the binding or the function of expressed α4β2 and α7 nAChRs.

Conclusion: Our results support the potential of L-theanine as a promising candidate for treating nicotine dependence.

Keywords: Conditioned place preference; L-theanine; Mice; Nicotine; Nicotinic receptors; Withdrawal.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Humans
  • Male
  • Mecamylamine / pharmacology
  • Mice
  • Mice, Inbred ICR
  • Nicotine / pharmacology
  • Nicotine / therapeutic use
  • Nicotinic Antagonists / pharmacology
  • Receptors, Nicotinic* / physiology
  • Reward
  • Substance Withdrawal Syndrome* / psychology

Substances

  • Nicotine
  • theanine
  • Receptors, Nicotinic
  • Mecamylamine
  • Nicotinic Antagonists