Riluzole rapidly attenuates hyperemotional responses in olfactory bulbectomized rats, an animal model of depression.
Growing evidence indicates that the glutamatergic neurotransmitter system is central to the neurobiology and treatment of depression. Riluzole, a drug currently used to slow the progression of amyotrophic lateral sclerosis (ALS), directly affects the glutamatergic system. In this study, we investigated the effects of riluzole in olfactory bulbectomy (OBX) rats, an animal model of depression. The olfactory bulbs in rats were removed by suction. The emotionality of rats was measured by scoring their responses to given stimuli, i.e., attack, startle, struggle, and fight responses. The OBX rats chronically treated with vehicle for 7 days at 14 days following surgery showed significant increases in emotionality responses. Single (1st day administration) and subchronic (7th day administration) riluzole treatment (1-10 mg/kg, po) significantly and dose-dependently reduced hyperemotional responses in OBX rats. Both single and subchronic riluzole treatment (10 mg/kg, po) had no significant effects on the emotional responses in sham operated rats. In addition, we demonstrated that single riluzole treatment (10 mg/kg, po) significantly decreased extracellular glutamate levels in medial prefrontal cortex of OBX rats by in vivo microdialysis. We provide the first experimental evidence that riluzole rapidly attenuated hyperemotional responses in OBX rats, an animal model of depression.
Takahashi
Kou
K
Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashimachi, Kodaira, Tokyo 187-8553, Japan.
Murasawa
Hiroyasu
H
Yamaguchi
Kazumasa
K
Yamada
Misa
M
Nakatani
Akiko
A
Yoshida
Masumi
M
Iwai
Takashi
T
Inagaki
Masatoshi
M
Yamada
Mitsuhiko
M
Saitoh
Akiyoshi
A
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003866:Depressive Disorder / Q000188:drug therapy*; D004195:Disease Models, Animal; D004644:Emotions / Q000187:drug effects*; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009830:Olfactory Bulb / Q000601:surgery*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019782:Riluzole / Q000494:pharmacology* / Q000627:therapeutic use; D018709:Statistics, Nonparametric
D018698:Glutamic Acid; D019782:Riluzole