Iwamoto E T, Loh H H, Way E L
Eur J Pharmacol. 1976 Jun;37(2):339-56. doi: 10.1016/0014-2999(76)90042-x.
Unilateral destruction of dopaminergic cell bodies in the substantia nigra zona compacta (SNC) was performed in rats using either electrocoagulation or chemical lesioning (6-hydroxydopamine, 6-OHDA). Neostriatal dopamine concentration ipsilateral to an electrolytic lesion was 34% of the contralateral side 2-3 weeks after operation; serotonin and noradrenaline brain levels were not altered. In contrast, dopamine and noradrenaline forebrain concentrations ipsilateral to a 6-OHDA lesion were 20 and 31%, respectively, of the contralateral side. After 6-OHDA, dopamine concentrations in the ipsilateral neostriatum were reduced to levels below the sensitivity of the fluorometric assay; cortical, brainstem and neostriatal serotonin levels, on the other hand, were not altered after 6-OHDA. Ipsilateral circling behavior was elicited by d-amphetamine after electrolytic and chemical lesioning. In contrast, the direction of circling produced after apomorphine differed between the two lesion models: contralateral circling behavior was exhibited by 6-OHDA-lesioned rats, whereas ipsilateral circling was produced in animals with electrolytic lesions. Contralateral circling was induced in both lesion-type models by haloperidol or pimozide. S.c. atropine administration induced ipsilateral circling in rats with 6-OHDA lesions, whereas contralateral circling was observed after arecoline. Animals with electrolytic SNC lesions turn ipsilaterally after s.c. administrations of either arecoline or atropine. The data indicate that the electrolytic and 6-OHDA circling behavior models represent two different neuropharmacological states and it is, therefore, suggested that comparisons of data obtained from models using different methods of lesioning be made with caution.
使用电凝法或化学损伤法(6-羟基多巴胺,6-OHDA)在大鼠中对黑质致密部(SNC)的多巴胺能细胞体进行单侧破坏。术后2-3周,电解损伤同侧新纹状体中的多巴胺浓度为对侧的34%;血清素和去甲肾上腺素的脑内水平未改变。相比之下,6-OHDA损伤同侧的多巴胺和去甲肾上腺素前脑浓度分别为对侧的20%和31%。6-OHDA处理后,同侧新纹状体中的多巴胺浓度降至低于荧光测定法的灵敏度水平;另一方面,6-OHDA处理后,皮质、脑干和新纹状体中的血清素水平未改变。电解损伤和化学损伤后,d-苯丙胺均可引发同侧转圈行为。相比之下,两种损伤模型中阿扑吗啡诱导的转圈方向不同:6-OHDA损伤的大鼠表现出对侧转圈行为,而电解损伤的动物则产生同侧转圈。氟哌啶醇或匹莫齐特在两种损伤类型模型中均诱导对侧转圈。皮下注射阿托品可使6-OHDA损伤的大鼠产生同侧转圈,而槟榔碱注射后则观察到对侧转圈。电解损伤SNC的动物在皮下注射槟榔碱或阿托品后会向同侧转动。数据表明,电解损伤和6-OHDA转圈行为模型代表两种不同的神经药理学状态,因此,建议谨慎比较使用不同损伤方法的模型所获得的数据。