Sleep-promoting effects of a GABA/5-HTP mixture: Behavioral changes and neuromodulation in an invertebrate model

Life Sci. 2016 Apr 1;150:42-9. doi: 10.1016/j.lfs.2016.02.086. Epub 2016 Feb 26.


Aims: This study was to investigate the sleep promoting effects of combined γ-aminobutyric acid (GABA) and 5-hydroxytryptophan (5-HTP), by examining neuronal processes governing mRNA level alterations, as well as assessing neuromodulator concentrations, in a fruit fly model.

Main methods: Behavioral assays were applied to investigate subjective nighttime activity, sleep episodes, and total duration of subjective nighttime sleep of two amino acids and GABA/5-HTP mixture with caffeine treated flies. Also, real-time PCR and HPLC analysis were applied to analyze the signaling pathway.

Key findings: Subjective nighttime activity and sleep patterns of individual flies significantly decreased with 1% GABA treatment in conjunction with 0.1% 5-HTP treatment (p<0.001). Furthermore, GABA/5-HTP mixture resulted in significant differences between groups related to sleep patterns (40%, p<0.017) and significantly induced subjective nighttime sleep in the awake model (p<0.003). These results related to transcript levels of the GABAB receptor (GABAB-R1) and serotonin receptor (5-HT1A), compared to the control group. In addition, GABA/5-HTP mixture significantly increased GABA levels 1h and 12h following treatment (2.1 fold and 1.2 fold higher than the control, respectively) and also increased 5-HTP levels (0 h: 1.01 μg/protein, 12h: 3.45 μg/protein).

Significance: In this regard, we successfully demonstrated that using a GABA/5-HTP mixture modulates subjective nighttime activity, sleep episodes, and total duration of subjective nighttime sleep to a greater extent than single administration of each amino acid, and that this modulation occurs via GABAergic and serotonergic signaling.

Keywords: 5-Hydroxytryptophan; Drosophila melanogaster; Insomnia; Sleep; γ-Aminobutyric acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Hydroxytryptophan / pharmacology*
  • Animals
  • Behavior, Animal / drug effects*
  • Caffeine / pharmacology
  • Central Nervous System Stimulants / pharmacology
  • Drosophila melanogaster*
  • Hypnotics and Sedatives / pharmacology*
  • Motor Activity / drug effects
  • Neurotransmitter Agents / pharmacology
  • Receptor, Serotonin, 5-HT1A / biosynthesis
  • Receptors, GABA-B / biosynthesis
  • Signal Transduction / drug effects
  • Sleep / drug effects*
  • gamma-Aminobutyric Acid / metabolism
  • gamma-Aminobutyric Acid / pharmacology*


  • Central Nervous System Stimulants
  • Hypnotics and Sedatives
  • Neurotransmitter Agents
  • Receptors, GABA-B
  • Receptor, Serotonin, 5-HT1A
  • Caffeine
  • gamma-Aminobutyric Acid
  • 5-Hydroxytryptophan