Behavioural and neurochemical features of olfactory bulbectomized rats resembling depression with comorbid anxiety.
In order to probe the nature and validity of olfactory bulbectomized (OB) rats as a model of depression, we reevaluated their behavioural and neurochemical deficits in relation to the symptoms and neurochemical abnormalities of depression using our protocols, which distinguish anhedonia-resembling behaviour in sexual behavioural test, the hippocampus (Hip)-dependent long-term memory and anxiety-resembling behaviour specially. Besides exploratory hyperactivity in response to a novel environmental stress resembling the psychomotor agitation, OB rats showed a decrease of libido, and a deficit of long-term explicit memory, resembling loss of interest and cognitive deficits in depressive patients, respectively. OB rats also exhibited the anxiety symptom-resembling behaviour in social interaction and plus-maze tests. In the OB rats, we found degenerated neurons in the piriform cortex, decreased protein expression of NMDA receptor subunit 1 (NR1), but not NR2A or NR2B, in the prefrontal cortex (PFC), Hip and amygdala (Amg), and decreased phosphorylation of cAMP-response element-binding protein (CREB) in the PFC and Hip, but not Amg. The behavioural and neurochemical abnormalities in OB rats, except for the performance in the plus-maze task and neuronal degeneration, were significantly attenuated by repeated treatment with desipramine (10 mg/kg), a typical antidepressant. The present study indicated that OB rats may be a model of depression with comorbid anxiety, characterized by agitation, sexual and cognitive dysfunction, neuronal degeneration, decreased protein expression of NR1, and decreased phosphorylation of CREB.
Wang
Dayong
D
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.
Noda
Yukihiro
Y
Tsunekawa
Hiroko
H
Zhou
Yuan
Y
Miyazaki
Masayuki
M
Senzaki
Koji
K
Nabeshima
Toshitaka
T
D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000150:complications / Q000503:physiopathology*; D003866:Depressive Disorder / Q000150:complications / Q000503:physiopathology*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009830:Olfactory Bulb / Q000502:physiology* / Q000601:surgery; D009833:Olfactory Pathways / Q000502:physiology*; D017397:Prefrontal Cortex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012919:Social Behavior
C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate