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

Background/IntroductionPrevious studies have investigated the neuroprotective effects of tamoxifen (TMX), but its antidepressant-like effects in traumatic brain injury (TBI) remain unclear.Purposes/AimsThe 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).MethodsAnesthetized 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.ResultsOn 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.ConclusionOur 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.