title: Short-term effects of melatonin and pinealectomy on serotonergic neuronal activity across the light-dark cycle.
abstract: 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.
authors: Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, QC, Canada.
authors: Sergio
authors: S
authors: Domínguez-López
authors: Ian
authors: I
authors: Mahar
authors: Francis Rodriguez
authors: FR
authors: Bambico
authors: Benoit
authors: B
authors: Labonté
authors: Rafael
authors: R
authors: Ochoa-Sánchez
authors: Marco
authors: M
authors: Leyton
authors: Gabriella
authors: G
authors: Gobbi
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D019329:Idazoxan / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D019964:Mood Disorders / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D017440:Photoperiod; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044122:Receptor, Melatonin, MT1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D044123:Receptor, Melatonin, MT2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology
chemical_list: C114459:4-phenyl-2-propionamidotetraline; D058669:Adrenergic alpha-2 Receptor Antagonists; D010879:Piperazines; D011725:Pyridines; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D058829:Serotonin 5-HT1 Receptor Antagonists; D013764:Tetrahydronaphthalenes; D014363:Tryptamines; C057154:luzindole; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D008550:Melatonin; D019329:Idazoxan