Nutr Res Pract.  2018 Jun;12(3):208-214. 10.4162/nrp.2018.12.3.208.

Two combined amino acids promote sleep activity in caffeine-induced sleepless model systems

Affiliations
  • 1Department of Biological Sciences and Environmental Sciences Program, Southern Illinois University-Edwardsville, Edwardsville, IL 62026, United States.
  • 2Dongguk University Research Institute of Biotechnology and Medical Converged Science, Dongguk University, Gyeonggi 10325, Korea.
  • 3Department of Public Health Sciences, Korea University, 145 Anam-ro, Sungbuk-gu, Seoul 02841, Korea. suh1960@korea.ac.kr

Abstract

BACKGROUND/OBJECTIVES
The aim of this study was to evaluate the biological and sleep-promoting effects of combined γ-aminobutyric acid (GABA) and 5-hydroxytryptophan (5-HTP) using caffeine-induced sleepless fruit flies, ICR mice, and Sprague-Dawley rats.
MATERIALS/METHODS
Video-tracking analysis was applied to investigate behavioral changes of Drosophila melanogaster. Pentobarbital-induced sleep test and electroencephalogram (EEG) patterns were used for analysis of sleep latency, duration, and quantity and quality of sleep in vertebrate models.
RESULTS
Administration of combined GABA/5-HTP could significantly reverse the caffeine induced total distance of flies (P < 0.001). Also, individually administered and combined GABA/5-HTP significantly increased the total sleeping time in the caffeine-induced sleepless ICR mice (P < 0.001). In the caffeine-induced sleepless SD-rats, combined GABA/5-HTP showed significant differences in sleep quality between individual amino acid administrations (P < 0.05).
CONCLUSIONS
Taken together, we identified inhibitory effects of combined GABA/5-HTP in locomotor activity, sleep quantity and quality in caffeine-induced sleepless models, indicating that combined GABA/5-HTP may be effective in patients with insomnia by providing sufficient sleep.

Keyword

Sleep; caffeine; GABA; 5-HTP; insomnia

MeSH Terms

5-Hydroxytryptophan
Amino Acids*
Animals
Caffeine
Diptera
Drosophila melanogaster
Electroencephalography
Fruit
gamma-Aminobutyric Acid
Humans
Mice
Mice, Inbred ICR
Motor Activity
Rats, Sprague-Dawley
Sleep Initiation and Maintenance Disorders
Vertebrates
5-Hydroxytryptophan
Amino Acids
Caffeine
gamma-Aminobutyric Acid

Figure

  • Fig. 1 Effects of two amino acids and combined GABA/5-HTP on (A) the distance moved, (B) turn angle, and (C) mobility of Drosophila during the 5-min observation period in the open field assay. Values are mean ± SE (n = 90). Different letters indicate significant differences at P < 0.05 by Tukey's test and different symbols indicate significant differences at *P < 0.05, **P < 0.01, ***P < 0.001 by Dunnett's test. GABA, γ-aminobutyric acid; 5-HTP, 5-hydroxytryptophan.

  • Fig. 2 Effects of two amino acids and combined GABA/5-HTP on (A) meander and (B) velocity of Drosophila during the 5-min observation period in the open field assay. Values are means ± SE (n = 90). Different letters indicate significant differences at P < 0.05 by Tukey's test and different symbols indicate significant differences at *P < 0.05, **P < 0.01 by Dunnett's test. GABA, γ-aminobutyric acid; 5-HTP, 5-hydroxytryptophan.

  • Fig. 3 Effects of two amino acids and combined GABA/5-HTP on (A) sleep onset and (B) duration in caffeine-induced sleepless mice intraperitoneal injected a hypnotic dosage of pentobarbital (42 mg/kg, i.p.). Values are mean ± SE (n = 50). Different letters indicate significant differences at P < 0.05 by Tukey's test and different symbols indicate significant differences **P < 0.01, ***P < 0.001 by Dunnett's test. GABA, γ-aminobutyric acid; 5-HTP, 5-hydroxytryptophan.

  • Fig. 4 Effects of two amino acids and combined GABA/5-HTP on (A) wake, (B) sleep, (C) NREM and D) REM in caffeine-induced sleepless rats. Values are mean ± SE (n = 40). Different letters indicate significant differences at P < 0.05 by Tukey's test and different symbols indicate significant differences at * P < 0.05, ** P < 0.01 by Dunnett's test. GABA, γ-aminobutyric acid; 5-HTP, 5-hydroxytryptophan.


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