Chronic diazepam administration differentially affects melatonin synthesis in rat pineal and Harderian glands.
BACKGROUND
Pineal and Harderian gland melatonin production as well as plasma melatonin levels were investigated in male Wistar rats (12 weeks old) after administration of diazepam, a benzodiazepine widely used as anxiolytic.


OBJECTIVE
The present study investigates the effects of a chronic administration of diazepam on pineal and Harderian gland melatonin contents.


METHODS
Diazepam was administered subcutaneously, for 21 days, at a dosage of 3 mg/kg body weight per day, 1 h before the onset of darkness.


RESULTS
Diazepam clearly affected pineal melatonin biosynthesis and plasma melatonin levels. Diazepam reduced the pineal melatonin content (by a factor of 2) and the activity of N-acetyltransferase (NAT) (by a factor of 3.5), as well as plasma melatonin levels (by a factor of 1.5), but had no effects on pineal hydroxyindole-O-methyltransferase activity. By contrast to the pineal gland, diazepam failed to affect the Harderian gland melatonin content.


CONCLUSIONS
Our results suggest that the inhibition of melatonin production induced by diazepam in vivo may be due to a direct action of this benzodiazepine on the pineal gland, through its action on NAT, the key enzyme of melatonin synthesis, and that the control of melatonin production in the Harderian glands may be different from that observed in the pineal gland.
Djeridane
Y
Y
Service de Biochimie Médicale, Faculté de Médecine Pitié-Salpêtrière, 91 Boulevard de l'Hôpital, 75634 Paris, France.
Touitou
Y
Y
D000121:Acetylserotonin O-Methyltransferase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000187:drug effects / Q000378:metabolism; D003975:Diazepam / Q000008:administration & dosage*; D018757:GABA Modulators / Q000008:administration & dosage*; D006243:Harderian Gland / Q000187:drug effects* / Q000378:metabolism; D007279:Injections, Subcutaneous; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D010870:Pineal Gland / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D018757:GABA Modulators; D000121:Acetylserotonin O-Methyltransferase; D001191:Arylamine N-Acetyltransferase; D008550:Melatonin; D003975:Diazepam