Role for dopamine neurons of the rostral linear nucleus and periaqueductal gray in the rewarding and sensitizing properties of heroin
Role for dopamine neurons of the rostral linear nucleus and periaqueductal gray in the rewarding and sensitizing properties of heroin
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DOI：
10.1038/sj.npp.1300946
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发表时间：
2006-07-01
影响因子：
7.6
通讯作者：
Fernandez-Espejo, Emilio
中科院分区：
文献类型：
--
作者：
Flores, Juan A.;Galan-Rodriguez, Beatriz;Fernandez-Espejo, Emilio
腹侧被盖区（VTA）外存在中脑多巴胺能网络，包括吻侧线性核（RLi）和导水管周围灰质（PAG）等结构。这些核团投射到与药物强化效应有关的神经区域，表明它们可能参与阿片奖赏。目的是研究多巴胺网络的RLi/PAG区域的形态学特征，并辨别其作用的奖励和致敏作用的海洛因在大鼠中，多巴胺耗竭或局部注射多巴胺能拮抗剂。结果表明，这个网络是由小细胞的RLi/腹侧PAG，大多极多巴胺PAG神经元，和周围的导水管PAG神经元。重复海洛因后，大PAG神经元和小RLi/腹侧PAG细胞（不是导水管周围神经元）被激活，因为酪氨酸羟化酶被适应性诱导，而蛋白激酶A α没有变化。多巴胺耗竭后，小RLi/腹侧PAG神经元和大细胞的PAG（不periaqueductal的）的神经毒素的选择性影响。细胞计数显示，邻近腹侧被盖区和中缝背核的多巴胺神经元未受影响。损伤后，“焦虑样”反应和基础运动没有改变。然而，条件性位置偏好海洛因被发现被废除，以及海洛因诱导的运动敏感化。多巴胺能拮抗剂注入RLi/PAG后，D-2（而不是D-1）受体阻断剂量依赖性地消除海洛因诱导的奖励。本研究提供的证据表明，多巴胺神经元的RLi/PAG区域（不包括PAG导水管周围细胞）显示适应性的生化变化后，海洛因，并介导这种药物的奖励和敏化作用。RLi/PAG区域内的D-2多巴胺受体参与这些作用。
There is a mesencephalic dopaminergic network outside the ventral tegmental area (VTA), including structures such as the rostral linear nucleus (RLi) and periaqueductal gray (PAG). These nuclei project to neural areas implicated in reinforcing effects of drugs, indicating that they could participate in opiate reward. The objectives were to study the morphological characteristics of the dopamine network of the RLi/PAG region, and to discern its role on rewarding and sensitizing effects of heroin in rats, following dopamine depletion or local injection of dopaminergic antagonists. The findings indicated that this network is composed of small cells in the RLi/ventral PAG, large multipolar dopamine PAG neurons, and periaqueductal PAG neurons. Following repeated heroin, large PAG neurons and small RLi/ventral PAG cells (not periaqueductal neurons) were activated, since tyrosine-hydroxylase was adaptively induced, without changes in protein kinase A alpha. After dopamine depletion, small RLi/ventral PAG neurons and large cells of the PAG (not periaqueductal ones) were selectively affected by the neurotoxin. Dopamine neurons of the nearby VTA and dorsal raphe were not affected, as revealed by cell counting. After lesion, 'anxiety-like' responses and basal locomotion were not altered. However, conditioned place preference to heroin was found to be abolished, as well as heroin-induced motor sensitization. Following infusions of dopaminergic antagonists into RLi/PAG, D-2 (not D-1) receptor blocking dose-dependently abolished heroin-induced reward. The present study provides evidence that dopamine neurons of the RLi/PAG region (excluding PAG periaqueductal cells) show adaptive biochemical changes after heroin, and mediate the rewarding and sensitizing effects of this drug. D-2 dopamine receptors within the RLi/PAG region participate in these effects.