title: Antidepressant-like effects and possible mechanisms of amantadine on cognitive and synaptic deficits in a rat model of chronic stress.
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.
authors.affiliation: a College of Life Sciences and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University , Tianjin , PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Yu
authors.affiliation: a College of Life Sciences and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University , Tianjin , PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: a College of Life Sciences and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University , Tianjin , PR China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Chen
authors.affiliation: a College of Life Sciences and Key Laboratory of Bioactive Materials Ministry of Education, Nankai University , Tianjin , PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
mesh_terms: D000547:Amantadine / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015153:Blotting, Western; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism*; D003863:Depression / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D000547:Amantadine
keywords: Amantadine; NR2B; PSD-95; chronic stress; cognition; synaptic plasticity