, Volume 154, Issue 4, pp 403–407

Chronic diazepam administration differentially affects melatonin synthesis in rat pineal and Harderian glands

  • Yasmina Djeridane
  • Yvan Touitou
Original Investigation

DOI: 10.1007/s002130000631

Cite this article as:
Djeridane, Y. & Touitou, Y. Psychopharmacology (2001) 154: 403. doi:10.1007/s002130000631


Rationale: 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.

Diazepam Melatonin Pineal gland Harderian gland N-Acetyltransferase Hydroxyindole-O-methyltransferase

Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Yasmina Djeridane
    • 1
  • Yvan Touitou
    • 1
  1. 1.Service de Biochimie Médicale, Faculté de Médecine Pitié-Salpêtrière, 91 Boulevard de l'Hôpital, 75634 Paris Cedex 13, France