Depression and poor sleep: The effect of monoaminergic antidepressants in a pre-clinical model in rats

• Published in: Pharmacology, biochemistry and behavior Vol. 86; no. 3; pp. 468 - 476
• Main Authors: Sánchez, Connie, Brennum, Lise T., Stórustovu, Signe í, Kreilgård, Mads, Mørk, Arne
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.03.2007; Elsevier Science
• Subjects: Adult and adolescent clinical studies; Animals; Antidepressive Agents - pharmacology; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Depression; Depression - complications; Depression - drug therapy; Depression - physiopathology; Disease Models, Animal; EEG; Escitalopram; Humans; In Vitro Techniques; Male; Medical sciences; Mood disorders; Neuropharmacology; Norepinephrine - physiology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Rats, Wistar; Serotonin - physiology; Sleep; Sleep - drug effects; Sleep - physiology; Sleep disruption; Sleep Wake Disorders - drug therapy; Sleep Wake Disorders - etiology; Sleep Wake Disorders - physiopathology; Synaptosomes - drug effects; Synaptosomes - metabolism; Depression; Sleep; Escitalopram; EEG; Sleep disruption; Mood disorder; Animal model; Serotonin; Rat; Psychotropic; Rodentia; Electrophysiology; Electroencephalography; Reuptake inhibitor; Selective serotonin reuptake inhibitor; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal; Neurotransmitter; Antidepressant agent
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2007.01.006

The effects of five antidepressants (escitalopram, paroxetine, duloxetine, venlafaxine, and reboxetine) on the sleep architecture were investigated in freely moving rats in the light phase of a 12:12 h light:dark cycle following a single i.p. dose of antidepressant. Overall, paroxetine and escitalopram exhibited the least sleep disruptive profiles, whereas duloxetine, venlafaxine, and reboxetine increased the time spent awake and suppressed paradoxical sleep. Analysis of the EEG at 1 h intervals revealed only subtle differences from the overall picture. The effect of venlafaxine on disruption of sleep architecture could not be readily explained by its in vitro serotonin (5-HT) and noradrenaline (NA) reuptake inhibitory potencies. In vivo microdialysis experiments in the ventral hippocampus of freely moving rats revealed that venlafaxine affected the 5-HT and NA systems equally at the doses tested. Duloxetine (7.7 mg/kg) induced maximal blockade of the 5-HT transporter and duloxetine 7.7 mg/kg also modulated the noradrenaline system. Thus, in this animal model, the enhancement of noradrenergic activity is more disruptive on the sleep architecture than enhancement of serotonergic activity.