Behavioural and neurochemical features of olfactory bulbectomized rats resembling depression with comorbid anxiety

In order to probe the nature and validity of olfactory bulbectomized (013) 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. 013 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. (c) 2007 Elsevier B.V. All rights reserved.