R-citalopram prevents the neuronal adaptive changes induced by escitalopram.
This study examined the long-term effects of the antidepressant escitalopram on rat serotonin (5-HT) neuronal activity and hippocampal neuroplasticity. In the dorsal raphe nucleus, a 2-week treatment with escitalopram (10 mg/kg/day, subcutaneous) did not modify the firing activity of 5-HT neurons, whereas a cotreatment with R-citalopram (20 mg/kg/day, subcutaneous) decreased it. In the dentate gyrus of dorsal hippocampus, escitalopram increased significantly (57%) the number of de novo cells and this was prevented by a cotreatment with R-citalopram. The present results support the role of the allosteric modulation of the 5-HT transporter in the regulation of the recovery of 5-HT neuronal activity and long-lasting hippocampal cellular plasticity induced by escitalopram, two adaptive changes presumably associated with the antidepressant response.
Mnie-Filali
Ouissame
O
Laboratory of Neuropharmacology, Faculty of Pharmacy, University Lyon 1, Lyon Cedex, France.
Faure
Céline
C
Mansari
Mostafa El
ME
Lambás-Señas
Laura
L
Bérod
Anne
A
Zimmer
Luc
L
Sánchez
Connie
C
Haddjeri
Nasser
N
D000222:Adaptation, Physiological / Q000187:drug effects*; D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D015283:Citalopram / Q000737:chemistry / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D009435:Synaptic Transmission / Q000187:drug effects
D000928:Antidepressive Agents; D015283:Citalopram; D012701:Serotonin