Effects of tamoxifen on traumatic brain injury-induced depression in male rats

Background/Introduction: Previous studies have investigated the neuroprotective effects of tamoxifen (TMX), but its antidepressant-like effects in traumatic brain injury (TBI) remain unclear. Purposes/Aims: The present study was conducted to determine whether TMX can attenuate TBI-induced depression-like behavior and whether this effect involves the activation of extracellular signal-regulated kinase 1/2 (ERK1/2). Methods: Anesthetized male Sprague-Dawley rats were divided into four groups: sham-operated controls, TBI controls, TBI + TMX treatment (1 mg/kg), and TMX (1 mg/kg) + ERK1/2 antagonist, SL327 (30 mg/kg). Depression-like behaviors were evaluated through forced swim tests on Day 4, Day 8, and Day 15. On Day 15 after TBI, phosphorylated ERK1/2 (p-ERK1/2) expression was investigated by Western blotting; neuronal apoptosis, p-ERK1/2, B-cell chronic lymphocytic leukemia/lymphoma 2 (BCL2), and brain-derived neurotrophic factor (BDNF) expression in neuronal cells were evaluated using double immunofluorescence. Results: On Day 15 after TBI, TMX significantly reduced the duration of TBI-induced immobility compared with the TBI controls. The frequency of neuronal apoptosis and numbers of BCL2-positive, BDNF-positive, and p-ERK1/2-positive neuronal cells in hippocampal CA3 were significantly improved by TMX. However, these TMX effects were significantly blocked by SL327 administration. Conclusion: Our results suggest that intraperitoneal injection of TMX may ameliorate TBI-induced depression-like behavior in rats by increasing neuronal p-ERK1/2 expression, which may be associated with neuronal Bcl2 and BDNF expression and decreased neuronal apoptosis. This effect might represent a mechanism underlying the recovery from depression-like behavior. Copyright (C) 2016, Taiwan Surgical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).