Ketamine ameliorates severe traumatic event-induced antidepressant-resistant depression in a rat model through ERK activation

Publication date: Available online 30 March 2019Source: Progress in Neuro-Psychopharmacology and Biological PsychiatryAuthor(s): Chi-Wei Lee, Yi-Ju Chen, Han-Fang Wu, Yueh-Jung Chung, Yi-Chao Lee, Cheng-Ta Li, Hui-Ching LinAbstractTreatment-resistant depression (TRD) is a major public health issue, as it is common for patients with depression to fail to respond to adequate trials of antidepressants. However, a well-established animal model of TRD is still warranted. The present study focused on selective serotonin reuptake inhibitor (SSRI) resistance, and aimed to investigate whether higher levels of traumatic stress caused by greater numbers of foot-shocks may lead to severe depression and to examine the feasibility of this as an animal model of SSRI-resistant depression. To reveal the correlation between traumatic stress and severe depression, rats received 3, 6 and 10 tone (conditioned stimulus, CS)–shock (unconditioned stimulus, US) pairings to mimic mild, moderate, and severe traumatic events, and subsequent depressive-like behaviors and protein immunocontents were analyzed. The antidepressant efficacy was assessed for ketamine and SSRI (i.e., fluoxetine) treatment. We found that only the severe stress group presented depressive-like behaviors. Phosphorylation of extracellular signal-regulated kinases (ERKs) was decreased in the amygdala and prefrontal cortex (PFC). The immunocontents of GluA1 and PSD 95 were increased in the amygdala and decreased in the PFC. Moreover...
Source: Progress in Neuro Psychopharmacology and Biological Psychiatry - Category: Psychiatry Source Type: research