Bjelke B, Strömberg I, O'Connor W T, Andbjer B, Agnati L F, Fuxe K
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Brain Res. 1994 Oct 31;662(1-2):11-24. doi: 10.1016/0006-8993(94)90791-9.
In the present study the hypothesis has been tested if the dopamine releasing drug D-amphetamine via volume transmission can, at least partly, restore dopamine communication in the dopaminergically denervated neostriatum of rats. The experimental model used, has been a unilateral 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine neurons, based on nigral microinjections of this neurotoxin. Studies on c-fos like immunoreactivity after systemic D-amphetamine treatment demonstrated a wide-spread appearance of c-fos like immunoreactive neuronal nuclear profiles within the neostriatum on both the unlesioned and denervated side. In the unlesioned neostriatum a peak density of c-fos like immunoreactive profiles was found within the central part of the neostriatum, while on the denervated side the distribution pattern of c-fos like immunoreactive profiles peaked medially and gradually declined in a lateral direction. The microdialysis experiments demonstrated, after systemic d-amphetamine treatment, a marked and sustained increase of extracellular dopamine levels in the neostriatum on the unlesioned side, while no increases in the extracellular dopamine levels were observed on the dopaminergically denervated neostriatum. In the electrophysiological experiments, systemic D-amphetamine treatment produced an inhibition of the neuronal activity on the denervated side which showed a significant increase in basal discharge rate compared with the recordings obtained from the striata on the unlesioned side. The present immunocytochemical microdialysis and electrophysiological analysis provides evidence that in the unilaterally markedly dopamine depleted neostriatum with clearcut signs of dopamine receptor supersensitivity (rotational behaviour results), dopamine transmission may be partly restored via systemic D-amphetamine treatment through the release of dopamine, predominantly from the unlesioned neostriatum, which may diffuse into the cerebrospinal fluid to reach the contralateral dopaminergically denervated neostriatum.
在本研究中，已对多巴胺释放药物D-苯丙胺是否能通过容积传递至少部分恢复大鼠多巴胺能去神经支配的新纹状体中的多巴胺通讯这一假设进行了检验。所使用的实验模型是基于黑质微量注射这种神经毒素，由单侧6-羟基多巴胺诱导的黑质纹状体多巴胺神经元变性。对全身给予D-苯丙胺治疗后的c-fos样免疫反应性进行的研究表明，在未损伤侧和去神经支配侧的新纹状体内均广泛出现了c-fos样免疫反应性神经元核轮廓。在未损伤的新纹状体内，在新纹状体中部发现了c-fos样免疫反应性轮廓的峰值密度，而在去神经支配侧，c-fos样免疫反应性轮廓的分布模式在内侧达到峰值，并在外侧逐渐下降。微透析实验表明，全身给予d-苯丙胺治疗后，未损伤侧新纹状体内细胞外多巴胺水平显著且持续升高，而在多巴胺能去神经支配的新纹状体内未观察到细胞外多巴胺水平升高。在电生理实验中，全身给予D-苯丙胺治疗对去神经支配侧的神经元活动产生了抑制作用，与未损伤侧纹状体的记录相比，该侧基础放电率显著增加。目前的免疫细胞化学、微透析和电生理分析提供了证据，即在单侧明显多巴胺耗竭且有明确多巴胺受体超敏迹象（旋转行为结果）的新纹状体内，多巴胺传递可能通过全身给予D-苯丙胺治疗，主要从未损伤的新纹状体释放多巴胺，多巴胺扩散到脑脊液中到达对侧多巴胺能去神经支配的新纹状体而部分恢复。
