Carey M P, Diewald L M, Esposito F J, Pellicano M P, Gironi Carnevale U A, Sergeant J A, Papa M, Sadile A G
Laboratory Neurophysiology, Behaviour and Neural Networks, Department of Human Physiology F. Bottazzi, Napoli, Italy.
Behav Brain Res. 1998 Jul;94(1):173-85. doi: 10.1016/s0166-4328(97)00178-2.
The distribution of dopamine (DA) D-1 and D-2 receptors has been studied by autoradiography in the anterior forebrain of the pre-hypertensive spontaneously hypertensive rat (SHR) as an animal model of attention-deficit hyperactivity disorder (ADHD) in children. Juvenile male SHR and Wistar Kyoto (WKY) controls were given either vehicle or the DA re-uptake blocker methylphenidate (MP; 3 mg/kg, i.p.), daily during a 2-week period. A saturation analysis for the D-1 receptor subfamily was carried out with 0.1-5.0 nM of [3H]SCH23390 and two competition studies for the D-2 receptor subfamily with 4 nM of [3H]raclopride or 5 nM of [3H]quinpirole were carried out with unlabelled spiperone and 7-OH-DPAT as unlabelled displacers on cryostat coronal sections of the anterior forebrain. Quantitative receptor autoradiography and computer-assisted image analysis with reference to co-exposed 3H-microscale standards showed in vehicle-treated SHR higher density of DA D-1/D-5 receptor subtypes in the caudate-putamen (CPU), the nucleus accumbens (ACB) core and shell and the olfactory tubercle (OT), which was associated to a lower affinity. MP treatment normalised the DA D-1/D-5 receptors by decreasing the number of binding sites and increasing the affinity to control level. In addition, MP treatment 'down-regulated' DA D-2/D-4 subtypes in the CPU, ACB and OT, and 'up-regulated' mostly D-3 subtype in CPU, ACB, OT in both rat lines and in the globus pallidus, ventral pallidum and lateral septum in WKY rats only. In contrast, D-3 receptors were 'down-regulated' in the islands of Calleja in both rat lines. Moreover, regional cross-correlative analyses revealed a modulatory influence of DA receptors in the cross-talk within the anterior forebrain, which was altered in the SHR. Thus, the differential distribution and regulation of DA receptor subtypes following DA re-uptake blocker as well as the different regional cross-talk in the target sites of nigrostriatal and mesolimbic DA systems lend support to the DA hypothesis of ADHD in children.
作为儿童注意力缺陷多动障碍（ADHD）的动物模型，通过放射自显影术研究了高血压前期自发性高血压大鼠（SHR）前脑前部多巴胺（DA）D-1和D-2受体的分布。在为期2周的时间里，每天给幼年雄性SHR和Wistar Kyoto（WKY）对照大鼠注射溶剂或DA再摄取阻滞剂哌甲酯（MP；3mg/kg，腹腔注射）。用0.1-5.0nM的[3H]SCH23390对D-1受体亚家族进行饱和分析，并用4nM的[3H]雷氯必利或5nM的[3H]喹吡罗对D-2受体亚家族进行两项竞争研究，在未标记的螺哌隆和7-OH-DPAT作为未标记置换剂的情况下，对前脑的低温恒温冠状切片进行研究。定量受体放射自显影术和参照共同曝光的3H-微尺度标准的计算机辅助图像分析显示，在接受溶剂治疗的SHR中，尾状核-壳核（CPU）、伏隔核（ACB）核心和壳以及嗅结节（OT）中DA D-1/D-5受体亚型的密度较高，这与较低的亲和力相关。MP治疗通过减少结合位点数量并将亲和力提高到对照水平，使DA D-1/D-5受体正常化。此外，MP治疗使CPU、ACB和OT中的DA D-2/D-4亚型“下调”，并且仅在WKY大鼠的CPU、ACB、OT以及苍白球、腹侧苍白球和外侧隔中使大部分D-3亚型“上调”。相反，在两个大鼠品系的Calleja岛中，D-3受体“下调”。此外，区域交叉相关分析揭示了DA受体在前脑内部相互作用中的调节作用，而这种作用在SHR中发生了改变。因此，DA再摄取阻滞剂后DA受体亚型的差异分布和调节以及黑质纹状体和中脑边缘DA系统靶位点中不同的区域相互作用支持了儿童ADHD的DA假说。
