Eszopiclone and fluoxetine enhance the survival of newborn neurons in the adult rat hippocampus.
Clinical research has shown that co-administration of eszopiclone, a sedative-hypnotic sleeping agent, and fluoxetine, a serotonin uptake inhibitor, exerts an additive antidepressant action in treating patients with both depression and insomnia. Preclinical studies demonstrate that the behavioural actions of antidepressants are linked to neurogenesis in the adult hippocampus. To test the hypothesis that the additive effects of eszopiclone and fluoxetine could act via such a mechanism, the influence of combined administration of these agents on the proliferation and survival of bromodeoxyuridine (BrdU)-labelled newborn cells in the hippocampus of adult rats was determined. Chronic eszopiclone+fluoxetine co-administration significantly increased the survival, but not proliferation, of newborn neurons in dorsal hippocampus by approximately 50%, an effect greater than either drug alone. These findings are consistent with the hypothesis that eszopiclone enhances the antidepressant action of fluoxetine, in part via a novel mechanism that increases the survival of newborn neurons.
Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, CT 06508, USA.
Xiaowei W
XW
Su
Xiao-Yuan
XY
Li
Mounira
M
Banasr
Ronald S
RS
Duman
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004338:Drug Combinations; D000069582:Eszopiclone; D005473:Fluoxetine / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D053961:Azabicyclo Compounds; D004338:Drug Combinations; D010879:Piperazines; D005473:Fluoxetine; D000069582:Eszopiclone