Melatonin sees the light: blocking GABA-ergic transmission in the paraventricular nucleus induces daytime secretion of melatonin.
Despite a pronounced inhibitory effect of light on pineal melatonin synthesis, usually the daily melatonin rhythm is not a passive response to the surrounding world. In mammals, and almost every other vertebrate species studied so far, the melatonin rhythm is coupled to an endogenous pacemaker, i.e. a circadian clock. In mammals the principal circadian pacemaker is located in the suprachiasmatic nuclei (SCN), a bilateral cluster of neurons in the anterior hypothalamus. In the present paper we show in the rat that bilateral abolition of gamma-aminobutyric acid (GABA), but not vasopressin, neurotransmission in an SCN target area, i.e. the paraventricular nucleus of the hypothalamus, during (subjective) daytime results in increased pineal melatonin levels. The fact that complete removal of the SCN results in a pronounced increase of daytime pineal mRNA levels for arylalkylamine N-acetyltransferase (AA-NAT), i.e. the rate-limiting enzyme of melatonin synthesis, further substantiates the existence of a major inhibitory SCN output controlling the circadian melatonin rhythm.
Kalsbeek
A
A
Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam, The Netherlands.
Garidou
M L
ML
Palm
I F
IF
Van Der Vliet
J
J
Simonneaux
V
V
Pévet
P
P
Buijs
R M
RM
D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D001640:Bicuculline / Q000494:pharmacology; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D003714:Denervation; D018756:GABA Antagonists / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D008550:Melatonin / Q000378:metabolism*; D017551:Microdialysis; D009433:Neural Inhibition / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D010870:Pineal Gland / Q000201:enzymology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013493:Suprachiasmatic Nucleus / Q000378:metabolism / Q000601:surgery; D009435:Synaptic Transmission / Q000502:physiology*; D014667:Vasopressins / Q000378:metabolism / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018756:GABA Antagonists; D012333:RNA, Messenger; D014667:Vasopressins; D005680:gamma-Aminobutyric Acid; D001191:Arylamine N-Acetyltransferase; D008550:Melatonin; D001640:Bicuculline