Investigating the role of nisoldipine in foot‐shock‐induced post‐traumatic stress disorder in mice

Abstract

This study was designed to investigate the effectiveness of nisoldipine, an L-type voltage-sensitive calcium channel blocker, to ameliorate anxiety and fear response in a mouse model of post-traumatic stress disorder (PTSD). Acute trauma was induced in Swiss albino mice in a 2-day electric foot-shock paradigm consisting of 15 intermittent foot-shocks of 0.8 mA intensity, 10-s duration and 10-s intershock interval, during 5 min, followed by 3 weekly situational reminders, that is, once per week in the same context on three successive weeks. PTSD-induced behavioral changes were assessed using actophotometer, open-field, social interaction test, and freezing behavior. Biochemically, the serum corticosterone levels were estimated. Electric foot-shock and situational reminders produced behavioral alterations and decreased corticosterone levels, assessed on the 21st day following the traumatic event. Administration of sertraline (Ser 15 mg/kg), a selective serotonin reuptake inhibitor (SSRI) and nisoldipine (20 and 40 mg/kg), significantly attenuated the foot-shock-trauma-induced behavioral changes along with normalization of the corticosterone levels. It may be concluded that nisoldipine produces beneficial effects in re-establishing behavioral alterations, which may be due to normalization of reduced corticosterone levels in PTSD in mice.

Stimulation of Anxiety-Like Behavior via ERK Pathway by Competitive Serotonin Receptors 2A and 1A in Post-Traumatic Stress Disordered Mice

“…The ePet-Cre mice can express Cre recombinase in the serotonin neurons, Ai9 mice expressed the red fluorescent protein tdTomato because of the role of the Cre recombinant enzyme [34-36]. We found 300bp electrophoretic bands to be related to ePet-Cre in the PCR and agarose gel electrophoresis analyses.…”

“…The ePet-Cre-Ai9 mice were modeled to examine the function of serotonin on anxiety-like behavior [34-36]. The mice model was evaluated by open field test, freezing behavior test and the elevated plus maze test [22].…”

“…The PCR screening for TdTomato transgene integration was performed under the following conditions: 94℃ for 30 minutes, 36 cycles of 94℃ for 30 seconds, 61℃ for 30 seconds, 72℃ for 30 seconds, 72℃ for 2 minutes and kept at 4℃. PCR products were analyzed with agarose gel electrophoresis and visualized with Gel Image Analysis System (Tanon 2500R, Shanghai, China) [34-36]. …”

Epinephrine May Contribute to the Persistence of Traumatic Memories in a Post-traumatic Stress Disorder Animal Model

“…As previously described (Li et al, 2006;Zhang et al, 2012;Verma et al, 2016), mice were exposed to an aversive procedure consisting of two training sessions (day 0 and day 1). For the training sessions, we used a clear Plexiglass chamber with a metal grid floor, wired to a stimulus generator.…”

“…Several animal models have been developed using different types of traumatic events to study PTSD in humans (Pynoos et al, 1996). The PTSD animal model that we have selected is centered on the concept that exposure to foot shocks displays the pathophysiological process and the core symptomatology of PTSD, including freezing and anxiety-like behavior (Li et al, 2006;Zhang et al, 2012;Verma et al, 2016).…”