Wolterink G, Van Zanten E, Kamsteeg H, Radhakishun F S, Van Ree J M
Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht, The Netherlands.
Brain Res. 1990 Jan 15;507(1):101-8. doi: 10.1016/0006-8993(90)90527-i.
Functional recovery from motor hypoactivity of rats with 6-OHDA lesions in the nucleus accumbens is accelerated by intra-accumbal or subcutaneous treatment with the ACTH-(4-9) analog ORG 2766. The spontaneous recovery period of 3 weeks is shortened to 7 days by daily treatment with this peptide during the first 6 days after the lesion. The 6-OHDA lesion induced a decrease of about 30-40% in the levels of dopamine, HVA and DOPAC as well as in the uptake of [3H]dopamine in nucleus accumbens tissue in vitro. Treatment with ORG 2766 during the first 6 days following the lesion did not affect the lesion-induced changes in these biochemical parameters. Binding studies with [3H]haloperidol in nucleus accumbens tissue of placebo or ORG 2766-treated sham-lesioned rats revealed a linear Scatchard plot 7 days after the sham lesion. In tissue of placebo-treated 6-OHDA lesioned animals a similar linear Scatchard plot was found but in tissue of ORG 2766-treated 6-OHDA-lesioned rats the Scatchard plot was curvilinear in shape indicating two types of binding sites. In the 6-OHDA-lesioned rats treated with ORG 2766 the behavioral response upon apomorphine challenge was enhanced suggesting the existence of functional supersensitivity of the DA system. Similar changes in Scatchard plots and apomorphine-induced behavioral changes have been previously reported after spontaneous recovery. The present study indicates that ORG 2766 accelerates the process of functional recovery from impaired motor behavior of rats with 6-OHDA lesions in the nucleus accumbens, which may be due to development of denervation supersensitivity.
在伏隔核内或皮下注射促肾上腺皮质激素（4-9）类似物ORG 2766，可加速6-羟基多巴胺（6-OHDA）损伤大鼠伏隔核所致运动功能减退的恢复。在损伤后的前6天，每天用该肽治疗可将3周的自发恢复期缩短至7天。6-OHDA损伤导致体外伏隔核组织中多巴胺、高香草酸（HVA）和3,4-二羟基苯乙酸（DOPAC）水平以及[3H]多巴胺摄取量降低约30-40%。在损伤后的前6天用ORG 2766治疗并不影响损伤引起的这些生化参数的变化。对安慰剂或ORG 2766治疗的假损伤大鼠伏隔核组织进行[3H]氟哌啶醇结合研究，发现假损伤7天后的Scatchard图呈线性。在安慰剂治疗的6-OHDA损伤动物组织中发现了类似的线性Scatchard图，但在ORG 2766治疗的6-OHDA损伤大鼠组织中，Scatchard图呈曲线状，表明存在两种类型的结合位点。在用ORG 2766治疗的6-OHDA损伤大鼠中，阿扑吗啡激发后的行为反应增强，提示多巴胺（DA）系统存在功能性超敏反应。自发恢复后，此前曾报道过Scatchard图和阿扑吗啡诱导的行为变化有类似改变。本研究表明，ORG 2766可加速6-OHDA损伤大鼠伏隔核运动行为受损后的功能恢复过程，这可能是由于去神经超敏反应的发展所致。
