Thanellou Alexandra, Schachinger Kira M, Green John T
Department of Psychology, University of Vermont, Burlington, VT 05405-0134, USA.
Behav Neurosci. 2009 Jun;123(3):650-64. doi: 10.1037/a0015567.
Reductions in the volume of the cerebellum and impairments in cerebellar-dependent eyeblink conditioning have been observed in attention-deficit/hyperactivity disorder (ADHD). Recently, it was reported that subjects with ADHD as well as male spontaneously hypertensive rats (SHR), a strain that is frequently employed as an animal model in the study of ADHD, exhibit a parallel pattern of timing deficits in eyeblink conditioning. One criticism that has been posed regarding the validity of the SHR strain as an animal model for the study of ADHD is that SHRs are not only hyperactive but also hypertensive. It is conceivable that many of the behavioral characteristics seen in SHRs that seem to parallel the behavioral symptoms of ADHD are not solely due to hyperactivity but instead are the net outcome of the interaction between hyperactivity and hypertension. We used Wistar-Kyoto Hyperactive (WKHA) and Wistar-Kyoto Hypertensive (WKHT) rats (males and females), strains generated from recombinant inbreeding of SHRs and their progenitor strain, Wistar-Kyoto (WKY) rats, to compare eyeblink conditioning in strains that are exclusively hyperactive or hypertensive. We used a long-delay eyeblink conditioning task in which a tone conditioned stimulus was paired with a periorbital stimulation unconditioned stimulus (750-ms delay paradigm). Our results showed that WKHA and WKHT rats exhibited similar rates of conditioned response (CR) acquisition. However, WKHA males displayed shortened CR latencies (early onset and peak latency) in comparison to WKHT males. In contrast, female WKHAs and WKHTs did not differ. In subsequent extinction training, WKHA rats extinguished at similar rates in comparison to WKHT rats. The current results support the hypothesis of a relationship between cerebellar abnormalities and ADHD in an animal model of ADHD-like symptoms that does not also exhibit hypertension, and suggest that cerebellar-related timing deficits are specific to males.
在注意力缺陷多动障碍（ADHD）中，已观察到小脑体积减小以及依赖小脑的眨眼条件反射受损。最近有报道称，ADHD患者以及雄性自发性高血压大鼠（SHR）（一种在ADHD研究中经常用作动物模型的品系）在眨眼条件反射中表现出类似的时间缺陷模式。关于SHR品系作为ADHD研究动物模型的有效性，有人提出的一项批评是，SHR不仅多动，而且高血压。可以想象，在SHR中看到的许多行为特征似乎与ADHD的行为症状相似，并非仅仅由于多动，而是多动和高血压之间相互作用的最终结果。我们使用了Wistar-Kyoto多动（WKHA）和Wistar-Kyoto高血压（WKHT）大鼠（雄性和雌性），它们是通过SHR及其祖系Wistar-Kyoto（WKY）大鼠的重组近交产生的品系，以比较仅多动或仅高血压品系的眨眼条件反射。我们使用了一种长延迟眨眼条件反射任务，其中音调条件刺激与眶周刺激非条件刺激配对（750毫秒延迟范式）。我们的结果表明，WKHA和WKHT大鼠表现出相似的条件反应（CR）习得率。然而，与WKHT雄性相比，WKHA雄性的CR潜伏期缩短（起始和峰值潜伏期提前）。相比之下，雌性WKHA和WKHT没有差异。在随后的消退训练中，WKHA大鼠与WKHT大鼠的消退速度相似。目前的结果支持了在一个不伴有高血压的ADHD样症状动物模型中，小脑异常与ADHD之间存在关联的假设，并表明与小脑相关的时间缺陷在雄性中具有特异性。
