MRI Structure and Histological Change of Rat after Memantine Intake in Olfactory Bulbectomised Depression Model / 대한정신약물학회지

ABSTRACT

OBJECTIVE: The validity of olfactory bulbectomized rat as an animal depression model and the possibilities of the NMDA antagonist as an antidepressant would be evaluated by demonstrating structural alterations in their brain MRIs and histological findings of hippocampus. METHODS: Those 8-week old male Sprague-Dawley rats received either an olfactory bulbectomy or sham operation and volume changes at ventricles and caudate nucleus in their brain MRI were acquired at preoperation and postoperation. Those olfactory bulbectomized rats received either memantine, an uncompetitive NMDA antagonist, or normal saline, a placebo, and their brain structural changes in MRI were acquired. At preoperation, postoperation, and postmedication each one of the rats with sham-operation, with memantine, and with placebo was sacrificed to acquire histological impressions. RESULTS: 1) Comparison of the volume changes between preoperation and postoperation showed statistical significance; the volumes of the left and right lateral ventricles (p=0.007, p=0.008) and the third ventricle (p=0.003) increased significantly but the volumes of left and right caudate nucleus decreased (p=0.014, p=0.032), compared to that of the controls. 2) After 6-weeks of memantine administrations, the OB rats revealed more definite recovery in brain MRIs statistically than the controls: the volumes of left and right ventricles and left and right caudate nucleus (p=0.004, p=0.03 ; p=0.04, p=0.05). 3) The hippocampus histological findings of the olfactory bulbectomy showed frequently eosinophilic cytoplasm and hyperchromatic nucleus with shrinkage in CA3. After memantine intake, the hippocampus histological findings returned to nearly normal and showed mixtures of normal cell and abnormal neuron cell. CONCLUSION: The OB models would be valid as an animal model of depression and alterations in their brain MRI images after administrations of NMDA antagonist could be an indicator of antidepressant effects.