title: Sleep-promoting effects of a GABA/5-HTP mixture: Behavioral changes and neuromodulation in an invertebrate model.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Public Health Sciences, Korea University, Seoul 136-713, Republic of Korea.
authors.forename: Ki-Bae
authors.initials: KB
authors.lastname: Hong
authors.affiliation: Dongguk University Research Institute of Biotechnology, Goyang 10326, Republic of Korea. Electronic address: yooheonpark@dongguk.edu.
authors.forename: Yooheon
authors.initials: Y
authors.lastname: Park
authors.affiliation: Department of Public Health Sciences, Korea University, Seoul 136-713, Republic of Korea. Electronic address: suh1960@korea.ac.kr.
authors.forename: Hyung Joo
authors.initials: HJ
authors.lastname: Suh
mesh_terms: D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004331:Drosophila melanogaster; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000096:biosynthesis; D018080:Receptors, GABA-B / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D012890:Sleep / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000697:Central Nervous System Stimulants; D006993:Hypnotics and Sedatives; D018377:Neurotransmitter Agents; D018080:Receptors, GABA-B; D044282:Receptor, Serotonin, 5-HT1A; D002110:Caffeine; D005680:gamma-Aminobutyric Acid; D006916:5-Hydroxytryptophan
keywords: 5-Hydroxytryptophan; Drosophila melanogaster; Insomnia; Sleep; γ-Aminobutyric acid