Effects of milnacipran and fluvoxamine on hyperemotional behaviors and the loss of tryptophan hydroxylase-positive cells in olfactory bulbectomized rats.
BACKGROUND
It has been reported that many of the behavioral and serotonergic neuronal changes observed in olfactory bulbectomy (OBX) were improved by subchronic administration of a variety of antidepressants.


OBJECTIVE
We examined the effects of subchronic treatment with milnacipran, a dual serotonin and noradrenaline reuptake inhibitors (SNRIs) and fluvoxamine, selective serotonin reuptake inhibitors (SSRI) in the OBX-induced hyperemotional behaviors and tryptophan hydroxylase (TPH), rate-limiting enzyme of 5-HT.


METHODS
The olfactory bulbs were removed by suction. Drugs were administered p.o. once daily for 8 days beginning 14 days post-surgery. The hyperemotionality behaviors of OBX rats were measured by rating scale and in the elevated plus-maze test.


RESULTS
OBX rats, after milnacipran or fluvoxamine treatment, showed significant decrease in the score of hyperemotional responses on 7th day as compared with vehicle-treated OBX rats. In addition, milnacipran and fluvoxamine in OBX rats respectively produced a significant increase in the percentage of time spent in and number of entries into open arms in the elevated plus maze test. Furthermore, when 5-HTnergic neuronal function was examined using antibodies against tryptophan hydroxylase (TPH) following the behavioral tests, fluvoxamine significantly reversed the loss of TPH-positive cells produced by OBX in the dorsal raphe.


CONCLUSIONS
We demonstrated that chronic treatment with milnacipran or fluvoxamine was effective to improve both the hyperemotional behavior and the loss of TPH-positive cells seen in OBX rats.
Saitoh
Akiyoshi
A
Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo, 142-8501, Japan. a-saitoh@hoshi.ac.jp
Yamaguchi
Kazumasa
K
Tatsumi
Yoshimi
Y
Murasawa
Hiroyasu
H
Nakatani
Akiko
A
Hirose
Noritaka
N
Yamada
Misa
M
Yamada
Mitsuhiko
M
Kamei
Junzo
J
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003521:Cyclopropanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004644:Emotions / Q000187:drug effects*; D016666:Fluvoxamine / Q000494:pharmacology*; D008297:Male; D000078764:Milnacipran; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D009830:Olfactory Bulb / Q000601:surgery; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013997:Time Factors; D014365:Tryptophan Hydroxylase / Q000378:metabolism*
D018759:Adrenergic Uptake Inhibitors; D003521:Cyclopropanes; D016666:Fluvoxamine; D000078764:Milnacipran; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014365:Tryptophan Hydroxylase