Chronic Imipramine treatment increases the number of hippocampal neurons in a genetic rat depression model
Abstract
Neuronal plasticity in hippocampus plays an important role in the pathophysiology of depression and effects of antidepressant therapy. The aim of this study was to investigate whether chronic imipramine treatment on the Flinders Sensitive and Resistant Line (FSL/FRL) rats, a genetic rat model of depression, induces neuroplastic changes in hippocampus.
All rats were injected with imipramine or saline daily for 25 days. The volume and neuron numbers in hippocampus were estimated using design-based stereological methods.
Under untreated conditions, the volume and the number of neurons were significantly smaller in the FSL saline group (untreated “depressed†rats) compared to the FRL saline group (normal rats), showing correlation to the observed decreased immobility in the forced swim test. Imipramine treatment significantly increased the number of neurons in the granule cell layer (GCL) in CA1 in the FSL imipramine group (treated “depressed†rats) compared to the FSL saline group. The neurons number in the GCL and Hilus showed no differences in the FSL imipramine group compared to the FRL saline group.
In conclusions, baseline levels of the volume and the number of neurons in hippocampus were significantly smaller in the untreated FSL rats. Our findings indicate that chronic imipramine treatment reverses the suppression of neurogenesis in the hippocampus of the “depressed†FSL rats, and this occurs in correlation with behavioral effects. Our results support the neuronal plasticity hypothesis that depressive disorders may be related to impairments of structural plasticity and neuronal viability in hippocampus, and antidepressant treatment counteracts the structural impairments.
All rats were injected with imipramine or saline daily for 25 days. The volume and neuron numbers in hippocampus were estimated using design-based stereological methods.
Under untreated conditions, the volume and the number of neurons were significantly smaller in the FSL saline group (untreated “depressed†rats) compared to the FRL saline group (normal rats), showing correlation to the observed decreased immobility in the forced swim test. Imipramine treatment significantly increased the number of neurons in the granule cell layer (GCL) in CA1 in the FSL imipramine group (treated “depressed†rats) compared to the FSL saline group. The neurons number in the GCL and Hilus showed no differences in the FSL imipramine group compared to the FRL saline group.
In conclusions, baseline levels of the volume and the number of neurons in hippocampus were significantly smaller in the untreated FSL rats. Our findings indicate that chronic imipramine treatment reverses the suppression of neurogenesis in the hippocampus of the “depressed†FSL rats, and this occurs in correlation with behavioral effects. Our results support the neuronal plasticity hypothesis that depressive disorders may be related to impairments of structural plasticity and neuronal viability in hippocampus, and antidepressant treatment counteracts the structural impairments.
ISSN 1903-7236