Department of Psychology, Program in Neuroscience and CELEST Science of Learning Center, Boston University, Boston, Massachusetts 02215, USA.
Hippocampus. 2010 Jun;20(6):787-97. doi: 10.1002/hipo.20681.
The spontaneously hypertensive rat (SHR) is used as an animal model of attention deficit hyperactivity disorder (ADHD). It displays deficits in frontostriatal functioning, but it is unclear if medial temporal lobe functioning and structure are affected. We used behavioral tasks that evaluate functioning of the amygdala and hippocampus to compare male SHR to male rats from two inbred comparator strains, the normotensive Wistar-Kyoto (WKY) and the hypertensive Wistar-Kyoto (WKHT) rat (n = 8/strain). The three strains showed similar levels of amygdala-related stimulus-reward learning during conditioned cue preference testing. In the ambiguous T-maze task, which dissociates between spatial and habit learning, significantly more WKHT than SHR or WKY used a response (indicative of habit learning) versus a place (indicative of spatial learning) strategy during an early probe test on day 8. During a later probe test on day 24, WKY progressed significantly from using a place strategy to a response strategy. Throughout all probe tests, a place strategy was used predominately by SHR and a response strategy by WKHT. Thus, SHR exhibited deficits in dorsal striatum-related habit learning, whereas WKHT exhibited deficits in hippocampus-related spatial learning. Following behavioral testing, fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging scans were conducted in subgroups of rats from each strain (n = 4/strain). FLAIR imaging detected bilateral hippocampal hyperintensities in three of four WKHT and unilateral hippocampal atrophy in one of four SHR. The association between response strategy use during the initial probe test to forage for food in the ambiguous T-maze task and bilateral hippocampal abnormalities was significant. Collectively, while medial temporal lobe functioning appears to be normal in SHR exhibiting an ADHD-like phenotype, WKHT rats display both hippocampal functioning deficits and signs of bilateral hippocampal cell loss. The latter characteristics might be used to develop a new animal model of age- or disease-related decline in hippocampal functioning.
自发性高血压大鼠（SHR）被用作注意缺陷多动障碍（ADHD）的动物模型。它显示出额纹状体功能缺陷，但尚不清楚内侧颞叶功能和结构是否受到影响。我们使用了评估杏仁核和海马功能的行为任务，比较了雄性 SHR 与两种近交对照品系的雄性大鼠，即正常血压的 Wistar-Kyoto（WKY）和高血压的 Wistar-Kyoto（WKHT）大鼠（n = 8/品系）。这三种品系在条件性线索偏好测试中表现出相似水平的与杏仁核相关的刺激-奖励学习。在不确定 T 迷宫任务中，空间和习惯学习可以分离，在第 8 天的早期探针测试中，与 WKY 或 WKY 相比，明显更多的 WKHT 大鼠使用反应（表示习惯学习）而不是位置（表示空间学习）策略。在第 24 天的后期探针测试中，WKY 显著从使用位置策略转变为反应策略。在所有探针测试中，SHR 主要使用位置策略，WKHT 主要使用反应策略。因此，SHR 表现出与背侧纹状体相关的习惯学习缺陷，而 WKHT 表现出与海马体相关的空间学习缺陷。在行为测试之后，对每个品系的部分大鼠（n = 4/品系）进行了液体衰减反转恢复（FLAIR）磁共振成像扫描。FLAIR 成像在四只 WKHT 中的三只中检测到双侧海马体高信号，在四只 SHR 中的一只中检测到单侧海马体萎缩。在初始探针测试中，在不确定 T 迷宫任务中寻找食物时，反应策略的使用与双侧海马体异常之间存在显著关联。总的来说，虽然 SHR 表现出类似于 ADHD 的表型，但内侧颞叶功能似乎正常，但 WKHT 大鼠表现出海马体功能缺陷和双侧海马体细胞丢失的迹象。后者的特征可能被用于开发一种新的与年龄或疾病相关的海马体功能下降的动物模型。
