I'm reading a booklet on melatonin published in 1996, titled "Melatonin and the Biological Clock". This particular paragraph caught my attention and I would like to better understand what it means:

The requirement of intact beta-receptor function for melatonin synthesis, and the stimulatory effect of norepinephrine on melatonin synthesis and release, point up a theoretic relationship of melatonin to depression.

I've been looking at the biosynthesis of norepinephrine and tryptophan metabolism and do not see how the two cycles are connected. Is there a connection between the norepinephrine system and the melatonin synthesis in humans?

  • $\begingroup$ You might like to read papers which are more recent, as studies from 1996 do not include many recent findings on the interactions between NE and MEL. For example, a recent study finds there is an interaction between NE and MEL in the sleep-wake cycle. sciencedaily.com/releases/2012/06/120619225725.htm Although this doesn't directly describe a link between depresssion NE and MEL, it gives an interesting hint, since many depressive disorders include sleep problems. $\endgroup$
    – user16865
    Jul 20, 2015 at 20:44

1 Answer 1


This answer addresses your question about a link between norepinephrine and melatonin, but I have nothing to say about depression.

In vertebrates, the link between norepinephrine (NE) and melatonin lies in the regulation of the melatonin biosynthetic pathway.

Arylalkamine N-acetyltransferase (AANAT) is an enzyme in the biosynthetic pathway for melatonin, and controls the diurnal rhythm of melatonin production in the pineal gland. NE is released as a neurotransmitter by neurons innervating the pineal gland, and which themselves are regulated by the circadian pacemaker of the hypothalamus. One of the effects of NE on the pineal gland is to elevate the transcription of the AANAT gene via adrenoreceptors and cAMP levels.

The paper cited below describes this, and other relevant diurnal rhythms in the viscacha, a rodent of the chinchilla family. This animal was chosen because it has an interesting diurnal behaviour pattern with two apparent peaks in melatonin biosynthesis. It's a good starting point for further research into the literature on this topic.

Calderon,C et al. (2008) Daily rhythms of norepinephrine, β1-adrenoceptor mRNA, serotonin, arylalkylamine N-acetyltransferase mRNA, arylalkylamine N-acetyltransferase and hydroxyindol-O-methyltransferase activities, and melatonin in the pineal gland of viscacha. Biological Rhythm Research 39: 93-107

  • $\begingroup$ Thank you Alan! As far as I understand, there are two transferases, first AANAT and then HIOMT that are involved in Melatonin production from Serotonin. NE elevates the AANAT levels, influencing transormation of Serotonin to N-Acetyl-5-HT $\endgroup$
    – Alex Stone
    Sep 19, 2012 at 12:20

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