Role of the dopamine D3 receptor in reactivity to cocaine-associated cues in mice
Role of the dopamine D3 receptor in reactivity to cocaine-associated cues in mice
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DOI：
10.1046/j.1460-9568.2002.02049.x
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发表时间：
2002-06-01
影响因子：
3.4
通讯作者：
Sokoloff, P
中科院分区：
文献类型：
--
作者：
Le Foll, B;Francès, H;Sokoloff, P
先前与药物作用相关的环境刺激可以获得次级强化特性，能够维持药物寻求行为或诱导复发。我们已经使用了一个经典的巴甫洛夫条件反射程序来评估多巴胺D-3受体（D-3 R）在药物条件反射的表达中的作用。在与笼子不同的特定环境中重复接受可卡因的小鼠在随后暴露于药物配对环境后表现出过度运动。BP 897或SB-277011-A，D3 R选择性部分激动剂和拮抗剂，分别抑制可卡因条件性多动。D3 R基因靶向小鼠表现出可卡因线索条件性多动症增加的趋势。BP 897对中性或厌恶性线索的反应没有影响。可卡因处理的小鼠中脑腹侧被盖区（VTA）的D-3 R mRNA和结合水平增加，脑源性神经营养因子（BDNF）的转录水平增加，BDNF是一种控制D-3 R表达的因子。在饲养笼中给药时，考马斯亮蓝对D-3 R或BDNF基因没有影响。在皮质区，特别是在躯体感觉皮层，它被抑制BP 897，并在几个地区属于或连接到边缘系统的c-fos的表达被发现的条件。BP 897抑制条件反射小鼠腹侧被盖区c-fos的表达，激活杏仁核c-fos的表达。这些结果表明，可卡因线索的反应性的调制的D-3 R，其表达是升高的NAc的药物作用与一个特定的背景下，通过BDNF依赖性机制的重复关联。D-3 R选择性部分激动剂或拮抗剂抑制可卡因线索条件活动可能通过正常化加剧D-3 R功能的NAc，但我们的研究结果也指出了一个可能的参与途径，涉及腹侧被盖区，杏仁核和体感皮层。
Environmental stimuli previously associated with drug effects can acquire secondary reinforcing properties, able to maintain drug-seeking behaviour or induce relapse. We have used a classical Pavlovian conditioning procedure to assess the role of the dopamine D-3 receptor (D-3 R) in the expression of drug-conditioned responses. Mice repeatedly receiving cocaine in a particular environment distinct from home-cages displayed hyperlocomotion after subsequent exposure to the drug-paired environment. Cocaine-conditioned hyperactivity was inhibited by BP 897 or SB-277011-A, D3R-selective partial agonist and antagonist, respectively. D3R gene-targeted mice showed a trend towards an increase in cocaine cue-conditioned hyperactivity. BP 897 had no effect on reactivity to neutral or aversive cues. Cocaine-conditioned mice had increased levels of D-3 R mRNA and binding in the nucleus accumbens (NAc), and transcripts of brain-derived neurotrophic factor (BDNF), a factor controlling D-3 R expression, in the ventral tegmental area (VTA). Cocaine had no effects on D-3 R or BDNF genes when administered in home-cages. Cocaine cue-conditioned c-fos expression was found in cortical areas, notably in the somatosensory cortex, where it was inhibited by BP 897, and in several regions belonging or linked to the limbic system. In conditioned mice, BP 897 inhibited c-fos expression in VTA and activated it in amygdala. These results demonstrate a modulation of reactivity to cocaine cues by the D-3 R, the expression of which is elevated in the NAc by the repeated association of drug effects with a particular context, through a BDNF-dependent mechanism. D-3 R-selective partial agonist or antagonist inhibit cocaine cue-conditioned activity possibly by normalizing exacerbated D-3 R function in the NAc, but our results also point to a possible participation of a pathway involving the VTA, amygdala and somatosensory cortex.