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Neuropsychopharmacology. 2012 Nov;37(12):2702-11. doi: 10.1038/npp.2012.135. Epub 2012 Jul 25.

The same antidepressant elicits contrasting patterns of synaptic changes in the amygdala vs hippocampus.

Author information

1
National Centre for Biological Sciences, Bangalore, India.

Abstract

As depression-like symptoms are often precipitated by some form of stress, animal models of stress have been used extensively to investigate cellular mechanisms of depression. Despite being implicated in the emotional symptoms of depression, the amygdala has received little attention compared to the hippocampus in the past studies of antidepressant action. Further, these investigations have not taken into account the contrasting effects of chronic stress on the hippocampus vs amygdala. If an antidepressant is to be equally effective in countering the differential effects of stress on both brain areas, then it is faced with the challenge of eliciting contrasting effects in these two structures. We tested this prediction by examining the impact of tianeptine, an antidepressant with proven clinical efficacy, on neurons of the lateral amygdala (LA) and hippocampal area CA1. Tianeptine reduces N-methyl-D-aspartate (NMDA)-receptor-mediated synaptic currents, without affecting α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) currents, in LA neurons. By contrast, tianeptine enhances both NMDA and AMPA currents in area CA1. Tianeptine also lowers action potential firing in LA neurons. As tianeptine modulates cellular metrics that, in addition to mediating amygdalar behavioral output, are also affected by stress, we tested if tianeptine succeeds in countering stress effects in the intact animal. We find that tianeptine prevents two important functional consequences of chronic stress-induced plasticity in the amygdala--dendritic growth and enhanced anxiety-like behavior. These results provide evidence for antidepressant action on amygdalar neurons that are not only distinct from the hippocampus, but also protect against the debilitating impact of stress on amygdalar structure and function.

PMID:
22828748
PMCID:
PMC3473336
DOI:
10.1038/npp.2012.135
[Indexed for MEDLINE]
Free PMC Article

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