AMPA受体介导氯胺酮抗抑郁大鼠海马BDNF及TrkB变化

Changes of hippocampal BDNF and TrkB expression during AMPA receptors mediated ketamine-induced antidepressant effect in rats

目的观察α-氨基-3-羟基-5-甲基-4-异恶唑(AMPA)受体介导氯胺酮抗抑郁过程中大鼠海马脑源性神经营养因子(BDNF)及酪氨酸受体激酶B(TrkB)的表达变化。方法 80只Wistar雄性大鼠随机均分为八组:第一部分包括二甲基亚砜(DMSO)+生理盐水(V1组)、DMSO+氯胺酮(V2组)、AMPA受体阻断剂(NBQX)5mg/kg+氯胺酮(N5组)、NBQX10mg/kg+氯胺酮(N10组);第二部分包括DMSO+酒精+生理盐水(V3组)、DMSO+酒精+氯胺酮(V4组)、AMPA受体激动剂(CX546)1mg/kg+生理盐水(C0组)、CX5461mg/kg+氯胺酮组(C1组)。干预前1d大鼠强迫游泳15min,干预当天分别进行DMSO、NBQX及CX546预处理,30min后给予1ml生理盐水或氯胺酮10mg/kg。第2次给药后30min强迫游泳,记录5min内不动时间,随后取海马组织检测BDNF及TrkB表达。结果与V2组比较,N5组及N10组大鼠强迫游泳不动时间增加,海马BD-NF、TrkB表达减少(P<0.05)。与V4组比较,C1组大鼠强迫游泳不动时间减少,海马BDNF、TrkB表达增加(P<0.05)。结论 AMPA受体介导氯胺酮抗抑郁作用,这可能与海马组织中BDNF和TrkB表达上调有关。

Objective To observe the expression of hippocampal brain-derived neurotrophic factor （BDNF） and tyrosine receptor kinases B （TrkB） during AMPA receptors mediated ketamine-induced antidepressant effect in rats. Methods Eighty male Wistar rats were equally randomized into eight groups： Part 1 including DMSO＋saline （group V1）, DMSO＋ketamine （group V2）, AMPA receptor antagonist （NBQX） 5 mg/kg＋ketamine （group N5）, NBQX 10 mg/kg＋ketamine （group N10）; Part 2 including DMSO＋alcohol＋saline （group V3）, DMSC.） 2- alcohol -- ketamine （group V4）, AMPA receptor agonist （CX546） 1 mg/kg ＋ saline （ group C0 ）, CX546 1 mg/kg ＋ ketamine （ group C1 ）. One day before administration of drugs, rats were insulted in forced swimming test （FST） for 15 min. At the second day, rats were pretreated 1 ml of DMSO, Nt3QX and CX546, respectively. Thirty minutes after pretreatment, rats were intraperitoneally injected with 1 ml of saline or ketamine 10 mg/kg, respectively. Thirty minutes later after the second administration, 5min of FST was conducted and the immobility time of rats was recorded. Subsequently, the expression of hippocampal BDNF and TrkB were detected. Results Compared with group V2, rats showed significant increase of the ~ immobility time and decrease of the expression of hippocarnpal BDNF and TrkB in groups N5 and N10 （P〈0. 05）. Compared with group V4, rats showed significant decrease of the FST immobility time and increase of the expression of hippocampal BDNF and TrkB in group CI（P〈0. 05）. Conclusion AMPA receptors mediate the ketamine-induced antidepressant effect, which may be attributed to the changes in the expression of hippocampal BDNF and TrkB.