TY - JOUR
T1 - Lasting syndrome of depression produced by reduction in serotonin uptake during postnatal development
T2 - Evidence from sleep, stress, and behavior
AU - Popa, Daniela
AU - Léna, Clément
AU - Alexandre, Chloé
AU - Adrien, Joëlle
PY - 2008/4/2
Y1 - 2008/4/2
N2 - 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.
AB - 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.
KW - 5-HT transporter
KW - 5-HT1A autoreceptors
KW - Anxiety
KW - Corticosterone
KW - Depression
KW - Development
KW - Knock-out mice
KW - REM sleep
KW - Stress
UR - http://www.scopus.com/inward/record.url?scp=43649087841&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=43649087841&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.4006-07.2008
DO - 10.1523/JNEUROSCI.4006-07.2008
M3 - Article
C2 - 18385313
AN - SCOPUS:43649087841
SN - 0270-6474
VL - 28
SP - 3546
EP - 3554
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 14
ER -