GABA and l-theanine mixture decreases sleep latency and improves NREM sleep

Pharm Biol. 2019 Dec;57(1):65-73. doi: 10.1080/13880209.2018.1557698.

Abstract

Context: γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter and it is well established that activation of GABAA receptors favours sleep. l-Theanine, a naturally occurring amino acid first discovered in green tea, is a well-known anti-anxiety supplement with proven relaxation benefits.

Objective: This study investigated the potential synergistic sleep enhancement effect of GABA/l-theanine mixture.

Materials and methods: Pentobarbital-induced sleep test was applied to find proper concentration for sleep-promoting effect in ICR mice. Electroencephalogram (EEG) analysis was performed to investigate total sleeping time and sleep quality in normal SD rats and caffeine-induced awareness model. Real-time polymerase chain reaction (RT-PCR) was applied to investigate whether the sleep-promoting mechanism of GABA/l-theanine mixture involved transcriptional processes.

Results: GABA/l-theanine mixture (100/20 mg/kg) showed a decrease in sleep latency (20.7 and 14.9%) and an increase in sleep duration (87.3 and 26.8%) compared to GABA or theanine alone. GABA/l-theanine mixture led to a significant increase in rapid eye movement (REM) (99.6%) and non-REM (NREM) (20.6%) compared to controls. The use of GABA/l-theanine mixture rather than GABA or l-theanine alone restored to normal levels sleep time and quality in the arousal animal model. The administration of GABA/l-theanine led to increased expression of GABA and the glutamate GluN1 receptor subunit.

Conclusions: GABA/l-theanine mixture has a positive synergistic effect on sleep quality and duration as compared to the GABA or l-theanine alone. The increase in GABA receptor and GluN1 expression is attributed to the potential neuromodulatory properties of GABA/l-theanine combination, which seems to affect sleep behaviour.

Keywords: electroencephalography; insomnia; pentobarbital-induced sleep test; γ-Aminobutyric acid.

MeSH terms

  • Animals
  • Drug Synergism
  • Drug Therapy, Combination
  • Glutamates / pharmacology*
  • Mice
  • Mice, Inbred ICR
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glutamate / metabolism
  • Sleep Latency / drug effects*
  • Sleep, Slow-Wave / drug effects*
  • gamma-Aminobutyric Acid / pharmacology*

Substances

  • Glutamates
  • Receptors, Glutamate
  • gamma-Aminobutyric Acid
  • theanine

Grant support

This research was supported by the Ministry of Trade, Industry & Energy (MOTIE), Korea Institute for Advancement of Technology (KIAT) through the Encouragement Program for The Industries of Economic Cooperation Region (R0004012).