Lasting syndrome of depression produced by reduction in serotonin uptake during postnatal development: evidence from sleep, stress, and behavior.
Dysfunction of the serotonin system is implicated in sleep and emotional disorders. To test whether these impairments could arise during development, we studied the impact of early-life, transient versus genetic, permanent alterations of serotonin reuptake on sleep-wakefulness patterns, depression-related behavior, and associated physiological features. Here, we show that female mice treated neonatally with a highly selective serotonin reuptake inhibitor, escitalopram, exhibited signs of depression in the form of sleep anomalies, anhedonia, increased helplessness reversed by chronic antidepressant treatment, enhanced response to acute stress, and increased serotoninergic autoinhibitory feedback. This syndrome was not reproduced by treatment in naive adults but resembled the phenotype of mutant mice lacking the serotonin transporter, except that these exhibited decreased serotonin autoreceptor sensitivity and additional anxiety-like behavior. Thus, alteration of serotonin reuptake during development, whether induced by external or genetic factors, causes a depressive syndrome lasting into adulthood. Such early-life impairments might predispose individuals to sleep and/or mood disorders.
Popa
Daniela
D
Université Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche S677, F-75013 Paris, France. popa@ext.jussieu.fr
Léna
Clément
C
Alexandre
Chloé
C
Adrien
Joëlle
J
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000928:Antidepressive Agents / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D002755:Choice Behavior / Q000187:drug effects; D015283:Citalopram; D003345:Corticosterone / Q000097:blood; D003866:Depressive Disorder / Q000139:chemically induced / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000627:therapeutic use; D005518:Food Preferences / Q000187:drug effects; D007035:Hypothermia / Q000139:chemically induced; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000172:deficiency; D012893:Sleep Wake Disorders / Q000209:etiology*; D013057:Spectrum Analysis; D013312:Stress, Physiological / Q000188:drug therapy / Q000209:etiology*; D014851:Wakefulness / Q000187:drug effects
D000928:Antidepressive Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D005473:Fluoxetine; D015283:Citalopram; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003345:Corticosterone