Morissette M, Goulet M, Grondin R, Blanchet P, Bédard P J, Di Paolo T, Lévesque D
Unités 1d'Endocrinologie Moléculaire et de ; Facultés de 3Pharmacie et de, Québec, Canada, G1V 4G2.
Eur J Neurosci. 1998 Aug;10(8):2565-73. doi: 10.1046/j.1460-9568.1998.00264.x.
The role of the dopamine D3 receptor subtype in the central nervous system is still not well understood. It has a distinct and restricted distribution, mostly associated with limbic territories of the striatum (olfactory tubercle and the shell of nucleus accumbens) in rat brain. Dopaminergic denervation induced by a 6-hydroxydopamine lesion of the nigrostriatal system in rat down-regulates the expression of the D3 receptor. In the present study, we investigated the functional neuroanatomy of the dopamine D3 receptor subtype in the monkey (Macaca fascicularis) basal ganglia. We also studied the effect of administration of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and chronic D1-like (SKF 82958) or D2-like (cabergoline) agonist treatments on dopamine D3 receptor levels using receptor autoradiography. Our results clearly show that the distribution of D3 receptors in the monkey is more closely related to associative and limbic components of the striatum (caudate-putamen), as compared with its sensorimotor counterpart. Hence, D3 receptors may be more specifically involved in cognitive and motivational aspects of striatal functions, which are elaborated in prefrontal, temporal, parietal, cingulate and limbic cortices. Moreover, MPTP administration significantly decreased levels of D3 receptors and this effect was reversed or compensated by a chronic treatment with a D1-like, but not a D2-like, receptor agonist. The D3 receptor may represent an important target for adjunct or direct therapy designed to improve cognitive deficits observed in patients with Parkinson's disease, schizophrenia and other illnesses with frontal lobe cognitive disturbances.
多巴胺D3受体亚型在中枢神经系统中的作用仍未得到充分了解。它具有独特且受限的分布，在大鼠脑中主要与纹状体的边缘区域（嗅结节和伏隔核壳）相关。大鼠黑质纹状体系统的6-羟基多巴胺损伤诱导的多巴胺能去神经支配会下调D3受体的表达。在本研究中，我们调查了猕猴（食蟹猴）基底神经节中多巴胺D3受体亚型的功能神经解剖学。我们还使用受体放射自显影技术研究了给予多巴胺能神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）以及慢性给予D1样（SKF 82958）或D2样（卡麦角林）激动剂治疗对多巴胺D3受体水平的影响。我们的结果清楚地表明，与感觉运动对应部分相比，猕猴中D3受体的分布与纹状体（尾状核-壳核）的联合和边缘成分更密切相关。因此，D3受体可能更具体地参与纹状体功能的认知和动机方面，这些方面在前额叶、颞叶、顶叶、扣带回和边缘皮质中得到阐述。此外，给予MPTP会显著降低D3受体水平，而这种作用可通过慢性给予D1样受体激动剂而非D2样受体激动剂来逆转或补偿。D3受体可能是旨在改善帕金森病、精神分裂症和其他伴有额叶认知障碍疾病患者所观察到的认知缺陷的辅助或直接治疗的重要靶点。
