Sleep is closely related to the physiological state of the organisms and one-third of human life. Insomnia is a sleep disorder of difficult initiating or maintaining sleep and a common complaint in the general population. Over the past few decades, a considerable number of pharmacologic and non-pharmacologic treatment have been employed to regulate insomnia. Although there has been noticeable progress in the management of insomnia by using synthetic drugs, the side effects of these agents has increased the demand of natural products with sleep-promoting effects. Gamma-aminobutyric acid (GABA) and 5-hydroxytryptophan (5-HTP) are amino acids of digested nutrients or food ingredients and these can possibly be utilized as non-pharmacologic treatment for sleep disorder. It has been reported that each amino acid regulated the pattern and behavior of sleep, but the molecular mechanism responsible for GABA/5-HTP mixture underlying sleep-promoting effects are still unclear.
Two experiments in this study were designed to evaluate sleep-promoting effect of GABA/5-HTP mixture in invertebrate and vertebrate models, to clarify the possible ratio of sleep-promoting action in caffeine-induced awake models.
In an invertebrate, GABA/5-HTP mixture resulted in significant differences between groups with respect to sleep patterns. Dark phase activity and sleep episodes also decreased significantly in a caffeine-induced awake model (P < 0.01) and GABA/5-HTP mixture induced dark phase sleep in the awake model (P < 0.01). GABA/5-HTP mixture significantly increased transcript levels for the GABAB receptor and serotonin receptor, compared to the control group. GABA/5-HTP mixture significantly increased GABA levels 1 h and 12 h post-dose also increased 5-HTP levels (0 h: 1.01 μg/protein, 12 h: 3.45 μg/protein).
In a vertebrate, The GABA/5-HTP mixture significantly regulated the sleep latency and sleep duration in the sleep induced by sub-hypnotic and hypnotic dosages of pentobarbital (P < 0.05). In addition, the combination of GABA/5-HTP significantly increased the sleep quality than single administration of the amino acids (P < 0.05). Long-term administration of the GABA/5-HTP mixture increased the transcript levels of GABAA receptor (P < 0.05) and also increased the GABA content compared with the control group 12 h post-dose.
These available evidence suggests that the GABA/5-HTP mixture strongly modulates both GABAergic and serotonergic signaling. Moreover, the sleep architecture can be controlled by the regulation of GABAA receptor levels and GABA content with 5-HTP.