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Activation of hippocampal BDNF signaling is involved in the antidepressant-like effect of the NMDA receptor antagonist 7-chlorokynurenic acid.
- Source :
-
Brain Research . Jan2016, Vol. 1630, p73-82. 10p. - Publication Year :
- 2016
-
Abstract
- Previous studies showed that acute 7-chlorokynurenic acid treatment produced a rapid antidepressant-like action in depression-like animal models. However, the underlying mechanism involved in neurotrophin system about 7-chlorokynurenic acid is unclear. Our present study aimed to verify whether chronic 7-chlorokynurenic acid treatment produced an antidepressant-like effect through the activation of brain-derived neurotrophic factor (BDNF) signaling in mice exposed to chronic unpredictable mild stress (CUMS). In addition, we performed an oral toxicological evaluation of chronic 7-chlorokynurenic acid administration in mice. The results showed that a two-week administration with 7-chlorokynurenic acid reversed the decreased sucrose preference and prolonged first feeding latency. In addition, 7-chlorokynurenic acid significantly reversed the CUMS-induced down-regulation of BDNF, p-ERK, p-Akt, PSD-95, synapsin I and cell proliferation in the hippocampus. In contrast, K252a, an inhibitor of BDNF receptor tropomyosin-related kinase receptor B (TrkB), blocked the antidepressant-like effect and the improvement of 7-chlorokynurenic acid. Furthermore, we found that 7-chlorokynurenic acid did not produce any toxicological effect in mice. In conclusion, our findings suggest that the antidepressant-like effect of 7-chlorokynurenic acid may be mediated, at least in part, by activating BDNF signaling in the hippocampus. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00068993
- Volume :
- 1630
- Database :
- Academic Search Index
- Journal :
- Brain Research
- Publication Type :
- Academic Journal
- Accession number :
- 111440049
- Full Text :
- https://doi.org/10.1016/j.brainres.2015.11.005