Short-term effects of melatonin and pinealectomy on serotonergic neuronal activity across the light-dark cycle

J Psychopharmacol. 2012 Jun;26(6):830-44. doi: 10.1177/0269881111408460. Epub 2011 Jul 5.


Melatonin (MLT) and serotonin (5-HT) are two biosynthetically related compounds implicated in several common physiological functions and the etiology of mood disorders. How they interact, though, is not yet fully understood. In this study, single-unit extracellular recordings were used to monitor dorsal raphe nucleus (DR) 5-HT neuronal activity in anesthetized rats, under basal conditions (CTRL), in response to MLT administration, and after pinealectomy (PX) across the light-dark cycle. Under basal conditions, the number of spontaneously active 5-HT neurons and their firing rate were both significantly lower in the dark phase. In the light phase, administration of MLT at low doses (0.5-1 mg/kg, i.v.) decreased 5-HT firing activity. This inhibitory effect of MLT was completely blocked by the MT₁/MT₂ receptor antagonist luzindole, but not by the selective MT(2) receptor antagonist 4P-PDOT, the selective 5-HT(1A) receptor antagonist WAY100635, or by the α₂ adrenoceptor antagonist idazoxan. In the opposite experiment, PX increased 5-HT firing activity in the dark phase, and this was reversed by MLT administration (1 mg/kg, i.v.). Finally, in a forced swim test, MLT (1 mg/kg, i.p.) increased immobility time and decreased swimming behavior. Together, these results suggest that nocturnal MLT secretion imposes tonic inhibitory control over a sub-population of DR 5-HT neurons. This MLT-induced decrease in 5-HT neurotransmission may represent a biological mechanism underlying mood disorders characterized by increased MLT secretion, such as seasonal affective disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-2 Receptor Antagonists / pharmacology
  • Animals
  • Idazoxan / pharmacology
  • Male
  • Melatonin / metabolism*
  • Mood Disorders / metabolism
  • Mood Disorders / physiopathology
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / physiology*
  • Photoperiod*
  • Pineal Gland / drug effects
  • Pineal Gland / metabolism*
  • Pineal Gland / physiology
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Raphe Nuclei / drug effects
  • Raphe Nuclei / metabolism
  • Raphe Nuclei / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Melatonin, MT1 / antagonists & inhibitors
  • Receptor, Melatonin, MT1 / metabolism
  • Receptor, Melatonin, MT2 / antagonists & inhibitors
  • Receptor, Melatonin, MT2 / metabolism
  • Serotonin / metabolism*
  • Serotonin 5-HT1 Receptor Antagonists / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Tetrahydronaphthalenes / pharmacology
  • Tryptamines / pharmacology


  • 4-phenyl-2-propionamidotetraline
  • Adrenergic alpha-2 Receptor Antagonists
  • Piperazines
  • Pyridines
  • Receptor, Melatonin, MT1
  • Receptor, Melatonin, MT2
  • Serotonin 5-HT1 Receptor Antagonists
  • Tetrahydronaphthalenes
  • Tryptamines
  • luzindole
  • Serotonin
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • Melatonin
  • Idazoxan