Kline Anthony E, Wagner Amy K, Westergom Brian P, Malena Rebecca R, Zafonte Ross D, Olsen Adam S, Sozda Christopher N, Luthra Pallavi, Panda Monisha, Cheng Jeffery P, Aslam Haris A
Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA 15213, United States.
Behav Brain Res. 2007 Feb 27;177(2):186-94. doi: 10.1016/j.bbr.2006.11.036. Epub 2006 Dec 12.
Acute treatment with the 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) or chronic environmental enrichment (EE) hasten behavioral recovery after experimental traumatic brain injury (TBI). The aim of this study was to determine if combining these interventions would confer additional benefit. Anesthetized adult male rats received either a cortical impact or sham injury followed 15min later by a single intraperitoneal injection of 8-OH-DPAT (0.5mg/kg) or saline vehicle (1.0mL/kg) and then randomly assigned to either enriched or standard (STD) housing. Behavioral assessments were conducted utilizing established motor and cognitive tests on post-injury days 1-5 and 14-18, respectively. Hippocampal CA(1)/CA(3) neurons were quantified at 3 weeks. Both 8-OH-DPAT and EE attenuated CA(3) cell loss. 8-OH-DPAT enhanced spatial learning in a Morris water maze (MWM) as revealed by differences between the TBI+8-OH-DPAT+STD and TBI+VEHICLE+STD groups (P=0.0014). EE improved motor function as demonstrated by reduced time to traverse an elevated narrow beam in both the TBI+8-OH-DPAT+EE and TBI+VEHICLE+EE groups versus the TBI+VEHICLE+STD group (P=0.0007 and 0.0016, respectively). EE also facilitated MWM learning as evidenced by both the TBI+8-OH-DPAT+EE and TBI+VEHICLE+EE groups locating the escape platform quicker than the TBI+VEHICLE+STD group (P's<0.0001). MWM differences were also observed between the TBI+8-OH-DPAT+EE and TBI+8-OH-DPAT+STD groups (P=0.0004) suggesting that EE enhanced the effect of 8-OH-DPAT. However, there was no difference between the TBI+8-OH-DPAT+EE and TBI+VEHICLE+EE groups. These data replicate previous results from our laboratory showing that both a single systemic administration of 8-OH-DPAT and EE improve recovery after TBI and extend those findings by elucidating that the combination of treatments in this particular paradigm did not confer additional benefit. One explanation for the lack of an additive effect is that EE is a very effective treatment and thus there is very little room for 8-OH-DPAT to confer additional statistically significant improvement.
用5-羟色胺（1A）受体激动剂8-羟基-2-（二正丙基氨基）四氢化萘（8-OH-DPAT）进行急性治疗或长期进行环境富集（EE），可加速实验性创伤性脑损伤（TBI）后的行为恢复。本研究的目的是确定联合使用这些干预措施是否会带来额外益处。成年雄性大鼠在麻醉后接受皮层撞击或假手术损伤，15分钟后腹腔注射单次剂量的8-OH-DPAT（0.5mg/kg）或生理盐水载体（1.0mL/kg），然后随机分配到富集环境或标准（STD）环境饲养。分别在损伤后第1 - 5天和第14 - 18天，利用既定的运动和认知测试进行行为评估。在3周时对海马CA(1)/CA(3)神经元进行定量分析。8-OH-DPAT和EE均减轻了CA(3)细胞损失。如TBI + 8-OH-DPAT + STD组与TBI + 载体 + STD组之间的差异所示（P = 0.0014），8-OH-DPAT增强了在莫里斯水迷宫（MWM）中的空间学习能力。与TBI + 载体 + STD组相比，TBI + 8-OH-DPAT + EE组和TBI + 载体 + EE组穿越高架窄梁的时间减少，这表明EE改善了运动功能（分别为P = 0.0007和0.0016）。TBI + 8-OH-DPAT + EE组和TBI + 载体 + EE组定位逃生平台的速度均比TBI + 载体 + STD组更快，这证明EE也促进了MWM学习（P值均<0.0001）。在TBI + 8-OH-DPAT + EE组和TBI + 8-OH-DPAT + STD组之间也观察到MWM差异（P = 0.0004），这表明EE增强了8-OH-DPAT的效果。然而，TBI + 8-OH-DPAT + EE组和TBI + 载体 + EE组之间没有差异。这些数据重复了我们实验室之前的结果，即单次全身给予8-OH-DPAT和EE均能改善TBI后的恢复情况，并通过阐明在这种特定模式下联合治疗并未带来额外益处，扩展了这些发现。缺乏叠加效应的一种解释是，EE是一种非常有效的治疗方法，因此8-OH-DPAT几乎没有空间带来额外的统计学显著改善。
