Loupe Pippa S, Zhou Xiao, Davies Malonne I, Schroeder Stephen R, Tessel Richard E, Lunte Susan M
Schiefelbusch Institute for Life Span Studies, 1052 Dole Human Development Center, University of Kansas, Lawrence, KS 66045, USA.
Pharmacol Biochem Behav. 2002 Dec;74(1):61-71. doi: 10.1016/s0091-3057(02)00950-4.
Massed training in the conditional discrimination task, the fixed ratio discrimination (FRD) task led to elevated extracellular dopamine (DA) concentrations in the neonatal 6-hydroxydopamine (6-OHDA)-treated rat, a model of Lesch-Nyhan disease (LND). Rats neonatally treated with 6-OHDA or its vehicle were, as adults, implanted with microdialysis probes and assessed for basal pretraining concentrations of DA and its major metabolites. Subsequently, microdialysis samples were collected each day following three separate FRD training periods (trained group) or three separate periods of noncontingent food presentations (untrained group). The present study found that there were significant increases in extracellular DA in the caudate-putamen from basal pretraining concentrations in the repeated sample collections of trained 6-OHDA-lesioned animals but not in the samples of untrained 6-OHDA-lesioned animals. Consistent with previous studies [Brain Res. 508 (1990) 30.], there was an increase in the extracellular concentrations as compared to tissue concentrations of DA and 3,4-dihydroxyphenylacetic acid (DOPAC). Similar to our previous studies with long-term FRD training [Pharmacol. Biochem. Behav. 51 (1995) 861; Brain Res. 713 (1996) 246.], there was also an indication of an increase in cortical and striatal tissue concentration of DA in the trained 6-OHDA-lesioned animals as compared to the untrained 6-OHDA-lesioned animals. The elevations in striatal DA concentrations following operant performance in the present study illustrate how operant procedures of the behavior therapy used with individuals with LND and other mental retardation syndromes may interact with the modulation of dopaminergic function by the pharmaceutical application of DA antagonists to suppress aberrant behaviors.
在条件性辨别任务（固定比率辨别任务，FRD）中的集中训练导致新生6-羟基多巴胺（6-OHDA）处理的大鼠（一种莱施-尼汉病（LND）模型）细胞外多巴胺（DA）浓度升高。新生时用6-OHDA或其载体处理的大鼠成年后植入微透析探针，并评估DA及其主要代谢物的基础训练前浓度。随后，在三个单独的FRD训练期（训练组）或三个单独的非偶然性食物呈现期（未训练组）后的每天收集微透析样本。本研究发现，在重复收集的训练过的6-OHDA损伤动物样本中，尾状核-壳核中的细胞外DA与基础训练前浓度相比有显著增加，而在未训练的6-OHDA损伤动物样本中则没有。与先前的研究[《脑研究》508（1990）30]一致，与DA和3,4-二羟基苯乙酸（DOPAC）的组织浓度相比，细胞外浓度有所增加。与我们之前长期FRD训练的研究[《药理学、生物化学与行为》51（1995）861；《脑研究》713（1996）246]相似，与未训练的6-OHDA损伤动物相比，训练过的6-OHDA损伤动物的皮质和纹状体组织中DA浓度也有增加的迹象。本研究中操作性行为表现后纹状体DA浓度的升高说明了用于LND和其他智力发育迟缓综合征患者的行为疗法的操作性程序可能如何与DA拮抗剂的药物应用对多巴胺能功能的调节相互作用，以抑制异常行为。
