Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants.
Various chronic antidepressant treatments increase adult hippocampal neurogenesis, but the functional importance of this phenomenon remains unclear. Here, using genetic and radiological methods, we show that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants. Serotonin 1A receptor null mice were insensitive to the neurogenic and behavioral effects of fluoxetine, a serotonin selective reuptake inhibitor. X-irradiation of a restricted region of mouse brain containing the hippocampus prevented the neurogenic and behavioral effects of two classes of antidepressants. These findings suggest that the behavioral effects of chronic antidepressants may be mediated by the stimulation of neurogenesis in the hippocampus.
Santarelli
Luca
L
Center for Neurobiology and Behavior, Columbia University, New York, NY 10032, USA.
Saxe
Michael
M
Gross
Cornelius
C
Surget
Alexandre
A
Battaglia
Fortunato
F
Dulawa
Stephanie
S
Weisstaub
Noelia
N
Lee
James
J
Duman
Ronald
R
Arancio
Ottavio
O
Belzung
Catherine
C
Hen
René
R
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D003213:Conditioning, Psychological; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005239:Fear; D005247:Feeding Behavior / Q000187:drug effects; D005473:Fluoxetine / Q000494:pharmacology*; D006120:Grooming / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D017774:Long-Term Potentiation / Q000528:radiation effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D013312:Stress, Physiological / Q000188:drug therapy / Q000503:physiopathology; D009435:Synaptic Transmission / Q000528:radiation effects
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D005473:Fluoxetine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin