The improvement effect of TREK-1 potassium channel blockade on the behavior of depression model rats

Abstract

Objective To study the effect of TREK-1 potassium channel blocker on the behavior in rats with depression. Methods Forty-eight healthy adult male Sprague Dawley (SD) rats were divided into 6 groups as following: control + saline (CON group), control + fluoxetine (CON+ FLU group), control + SID1900 (CON+ SID group), CUMS + saline (CUMS group), CUMS + fluoxetine (CUMS+ FLU group) and CUMS + SID1900 (CUMS+ SID group) with 8 in each group. Isolated living conditions combining chronic unpredicted mild stress (CUMS) were used to establish depression model in rats. Four weeks after modeling, fluoxetine 10 mg·kg-1, SID1900 5.1 mg·kg-1 and 0.9% sodium chloride were given by intraperitoneal injection respectively. Body weight and behavioral performance of rats in several experiment paradigms were measured after drug administration. The behavioral paradigms included sucrose preference test(SPT), open field test(OFT) and forced swimming test(FST). Results Drug administration had no significant effect on body weight and behavioral performance in non stress rats (P>0.05), however, after chronic unpredicted mild stress the body weight, percentage of sucrose consumption, movement distances and rearing times in CUMS group were decreased dramatically contrast to CON group, but the immobility duration was increased significantly (all P<0.001). After treatment with drug for 14 days, the sucrose consumption percentage(62.03±6.99)%) and rearing times(18.57±6.37) in CUMS+ SID group were increased contrast to CUMS group((45.46±15.54)%, (5.83±3.06)), while the immobility time((123.57±26.73)s) was decreased compared with that in CUMS group((174.33±40.68)s). When drug administration for 28 days, the sucrose consumption percentage((79.64±11.37)%), the total distance as well as the rearing times ((13.18±3.17)m, (19.33±3.33)) within OFT in CUMS+ FLU group were increased in comparison with CUMS group((48.06±17.10)%, (4.45±3.69)m, (5.17±2.99)), and the immobility duration((97.83±18.97)s) in CUMS+ FLU group was shorter than that((194.83±37.97)s) in CUMS group(P<0.05). Notably, the immobility time in CUMS+ SID group ((44.29±14.30)s) was shortened obviously compared with that in CUMS+ FLU group((97.83±18.97)s)(P<0.01). Conclusion Blockade of TREK-1 potassium channel can ameliorate the depression-like behavior rapidly in rats. Key words: Depression; TREK-1 potassium channel; Chronic unpredicted mild stress; Behavior; SID1900