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| Content Provider | PubMed Central |
|---|---|
| Author | Luis, Nieto-gonzalez Jose Holm, Mai Marie Irina, Vardya Christensen, Trine Wiborg, Ove Jensen, Kimmo |
| Editor | Alexandra, Kavushansky |
| Copyright Year | 2015 |
| Abstract | Two main questions are important for understanding and treating affective disorders: why are certain individuals susceptible or resilient to stress, and what are the features of treatment response and resistance? To address these questions, we used a chronic mild stress (CMS) rat model of depression. When exposed to stress, a fraction of rats develops anhedonic-like behavior, a core symptom of major depression, while another subgroup of rats is resilient to CMS. Furthermore, the anhedonic-like state is reversed in about half the animals in response to chronic escitalopram treatment (responders), while the remaining animals are resistant (non-responder animals). Electrophysiology in hippocampal brain slices was used to identify a synaptic hallmark characterizing these groups of animals. Presynaptic properties were investigated at GABAergic synapses onto single dentate gyrus granule cells. Stress-susceptible rats displayed a reduced probability of GABA release judged by an altered paired-pulse ratio of evoked inhibitory postsynaptic currents (IPSCs) (1.48 ± 0.25) compared with control (0.81 ± 0.05) and stress-resilient rats (0.78 ± 0.03). Spontaneous IPSCs (sIPSCs) occurred less frequently in stress-susceptible rats compared with control and resilient rats. Finally, a subset of stress-susceptible rats responding to selective serotonin reuptake inhibitor (SSRI) treatment showed a normalization of the paired-pulse ratio (0.73 ± 0.06) whereas non-responder rats showed no normalization (1.2 ± 0.2). No changes in the number of parvalbumin-positive interneurons were observed. Thus, we provide evidence for a distinct GABAergic synaptopathy which associates closely with stress-susceptibility and treatment-resistance in an animal model of depression. |
| Related Links | http://dx.doi.org/10.1371/journal.pone.0119993 |
| Starting Page | 119993 |
| File Format | |
| ISSN | 19326203 |
| e-ISSN | 19326203 |
| Journal | PLoS ONE |
| Issue Number | 3 |
| Volume Number | 10 |
| Language | English |
| Publisher | Public Library of Science |
| Publisher Date | 2015-03-01 |
| Access Restriction | Open |
| Rights Holder | Public Library of Science |
| Subject Keyword | Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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