Papa M, Berger D F, Sagvolden T, Sergeant J A, Sadile A G
Institute Human Anatomy, Second University of Naples, Italy.
Behav Brain Res. 1998 Jul;94(1):197-211. doi: 10.1016/s0166-4328(97)00180-0.
The aim of this study was to trace by molecular imaging techniques the neural substrates of attention deficit hyperactivity disorder (ADHD) using the spontaneously hypertensive rat (SHR) as animal model. Adult SHR and Wistar-Kyoto (WKY) controls were used throughout this study. In experiment 1, naive male SHR and WKY were used, whereas in experiment 2 SHR and WKY rats of both genders were trained on a multiple fixed interval (FI (120 s for water, 5-min extinction)) paradigm and sacrificed 6 months later. In both experiments coronal sections of the anterior forebrain were processed for quantitative cytochrome oxidase (COase) histochemistry by the method of Gonzalez-Lima. Optical density values were transformed into actual enzyme activity units by using tissue-calibrated standards. In experiment 1, non-trained male rats of the SHR line showed lower COase activity in the medial and lateral prefrontal cortices, compared with WKY controls. In experiment 2, there was a line x treatment interaction effect in the pole of the nucleus accumbens (ACB). Regional correlative analyses revealed that: (i) under basal conditions, SHR are more synchronized than WKY rats in the COase level of different brain regions; and (ii) the training desynchronizes COase activity in the WKY, further synchronizes it and increases the cross-talk between hemispheres in male SHR only. Neurobehavioral covariations between behavioural scores and metabolic capacity in the medial and lateral prefrontal/frontal cortices, the caudate-putamen complex (CPU), the pole, core, and shell of the accumbal complex (ACB), and the ventral pallidum (VP), indicated that, in the WKY rats, the frequency of lever pressing covaried positively with the COase activity in the CPU, whereas in the SHR covaried with both medial and lateral prefrontal/frontal cortices. The bursts of activity during the 1-1.33-s segment was positively correlated, in the WKY rats only, with the core and shell of the ACB, and with the VP. Finally, the correlative profiles showed significant gender differences with effects in male SHR only. Thus, the results lend support to the involvement of the cortico-striato-pallidal system in ADHD.
本研究的目的是使用自发性高血压大鼠（SHR）作为动物模型，通过分子成像技术追踪注意力缺陷多动障碍（ADHD）的神经基质。在整个研究过程中使用成年SHR和Wistar-Kyoto（WKY）对照。在实验1中，使用未经训练的雄性SHR和WKY，而在实验2中，对两性的SHR和WKY大鼠进行多重固定间隔（FI（饮水120秒，5分钟消退））范式训练，并在6个月后处死。在两个实验中，均采用Gonzalez-Lima方法对前脑前部的冠状切片进行定量细胞色素氧化酶（COase）组织化学分析。通过使用组织校准标准将光密度值转换为实际酶活性单位。在实验1中，与WKY对照相比，SHR品系的未经训练的雄性大鼠在内侧和外侧前额叶皮质中显示出较低的COase活性。在实验2中，伏隔核（ACB）极存在品系x处理交互效应。区域相关性分析显示：（i）在基础条件下，SHR在不同脑区的COase水平上比WKY大鼠更同步；（ii）训练使WKY中的COase活性去同步，仅使雄性SHR中的COase活性进一步同步并增加半球间的串扰。内侧和外侧前额叶/额叶皮质、尾状核-壳核复合体（CPU）、伏隔核复合体（ACB）的极、核心和壳以及腹侧苍白球（VP）的行为评分与代谢能力之间的神经行为协变表明，在WKY大鼠中，压杆频率与CPU中的COase活性呈正相关，而在SHR中与内侧和外侧前额叶/额叶皮质均呈正相关。仅在WKY大鼠中，1-1.33秒时间段内的活动爆发与ACB的核心和壳以及VP呈正相关。最后，相关性图谱显示出显著的性别差异，仅在雄性SHR中有影响。因此，结果支持皮质-纹状体-苍白球系统参与ADHD。
