Antidepressant-like effects and possible mechanisms of amantadine on cognitive and synaptic deficits in a rat model of chronic stress. (2nd January 2016)

• Record Type: Journal Article
• Authors: Yu, Mei; Zhang, Yuan; Chen, Xiaoyu; Zhang, Tao
• Is Part Of: Stress. Volume 19:Number 1(2016:Jan.)
• Page Start: 104
• Page End: 113
• Publication Date: 2016-01-02
• Subjects: Amantadine -- chronic stress -- cognition -- synaptic plasticity -- NR2B -- PSD-95; Stress (Physiology) -- Periodicals; 616.98
• DOI: 10.3109/10253890.2015.1108302
• Languages: English
• ISSNs: 1025-3890

Abstract

Abstract: The aim of this study was to examine whether amantadine (AMA), as a low-affinity noncompetitive N -methyl-d -aspartate (NMDA) receptor antagonist, is able to improve cognitive deficits caused by chronic stress in rats. Male Wistar rats were divided into four groups: control, control + AMA, stress and stress + AMA groups. The chronic stress model combined chronic unpredictable stress (CUS) with isolated feeding. Animals were exposed to CUS continued for 21 days. AMA (25 mg/kg) was administrated p.o. for 20 days from the 4th day of CUS to the 23rd. Weight and sucrose consumption were measured during model establishing period. Spatial memory was evaluated using the Morris water maze (MWM) test. Following MWM testing, both long-term potentiation (LTP) and depotentiation were recorded in the hippocampal CA1 region. NR2B and postsynaptic density protein 95 (PSD-95) proteins were measured by Western-blot analysis. AMA increased weight and sucrose consumption of stressed rats. Spatial memory and reversal learning in stressed rats were impaired relative to controls, whereas AMA significantly attenuated cognitive impairment. AMA also mitigated the chronic stress-induced impairment of hippocampal synaptic plasticity, in which both the LTP and depotentiation were significantly inhibited in stressed rats. Moreover, AMA enhanced the expression of hippocampal NR2B and PSD-95 in stressed rats. The data suggest that AMA may be an effective therapeutic agent for depression-like symptoms and associated cognitive disturbances.