Activation of D₂-like receptors in rat ventral tegmental area inhibits cocaine-reinstated drug-seeking behavior.
Activation of D₂-like receptors in rat ventral tegmental area inhibits cocaine-reinstated drug-seeking behavior.
复制标题
DOI：
10.1111/j.1460-9568.2010.07591.x
复制
发表时间：
2011-04
期刊：
影响因子：
--
通讯作者：
Sun W
中科院分区：
文献类型：
--
作者：
Xue Y;Steketee JD;Rebec GV;Sun W
复发是可卡因成瘾的标志。可卡因诱导的皮质边缘中回神经可塑性改变是导致这一现象的关键因素。临床前证据表明，寻求可卡因行为的复发依赖于腹侧被盖区多巴胺神经元的激活。因此，阻止这种激活可能会抑制复发。由于多巴胺神经元的活动受躯体树突状细胞上表达的D2样自身受体的调节，本研究采用恢复模型，旨在确定腹侧被盖区D2样受体的激活是否能抑制可卡因诱导的消失的可卡因寻找行为的恢复。训练大鼠按改良的固定比例5程序静脉注射可卡因(0.25 mg/次)。在这种行为被很好地学习后，大鼠经过灭绝训练来消除寻找可卡因的行为。然后观察腹侧被盖区微量注射选择性D2受体激动剂奎比罗对可卡因诱导的恢复的影响。昆比罗(0-3.2gg/侧)可剂量依赖性地降低可卡因诱导的恢复，这种作用可被选择性D2受体拮抗剂依替氯必利逆转，当向腹侧被盖区微量注射奎比罗时，这种作用被逆转。这种效应似乎仅限于腹侧被盖区，因为向黑质微量注射喹比罗没有任何作用。由于D2样受体在投射到前额叶皮质和伏核的大鼠腹侧被盖区多巴胺神经元上表达，我们的数据表明这些多巴胺回路可能在可卡因诱导的恢复过程中发挥关键作用。讨论了D2样受体和多巴胺神经元相关信号分子的电位变化在复发易感性中的作用。
Relapse is a hallmark of cocaine addiction. Cocaine-induced neuroplastic changes in the mesocorticolimbic circuits critically contribute to this phenomenon. Preclinical evidence indicates that relapse to cocaine-seeking behavior depends on activation of dopamine neurons in the ventral tegmental area. Thus, blocking such activation may inhibit relapse. Because activity of dopamine neurons are regulated by D2-like autoreceptors expressed on somatodendritic sites, this study, using the reinstatement model, aimed to determine whether activation of D2-like receptors in the ventral tegmental area can inhibit cocaine-induced reinstatement of extinguished cocaine-seeking behavior. Rats were trained to self-administer intravenous cocaine (0.25 mg/infusion) under a modified fixed-ratio 5 schedule. After such behavior was well learned, rats went through extinction training to extinguish cocaine-seeking behavior. Then the effect of quinpirole, a selective D2-like receptor agonist microinjected into the ventral tegmental area on cocaine-induced reinstatement was assessed. Quinpirole (0 – 3.2 μg/side) dose-dependently decreased cocaine-induced reinstatement and such effects were reversed by the selective D2-like receptor antagonist eticlopride when co-microinjected with quinpirole into the ventral tegmental area. The effect appeared to be specific to the ventral tegmental area because quinpirole microinjected into the substantia nigra had no effect. Because D2-like receptors are expressed on rat ventral tegmental area dopamine neurons projecting to the prefrontal cortex and nucleus accumbens, our data suggest that these dopamine circuits may play a critical role in cocaine-induced reinstatement. The role of potential changes in D2-like receptors and related signaling molecules of dopamine neurons in the vulnerability to relapse was discussed.
登录
查看更多内容
影响因子：
7.6
作者：
Nader, MA;Daunais, JB;Porrino, LJ
通讯作者：
Porrino, LJ
影响因子：
16.2
作者：
Lammel, Stephan;Hetzel, Andrea;Roeper, Jochen
通讯作者：
Roeper, Jochen
影响因子：
5.3
作者：
Carr, DB;Sesack, SR
通讯作者：
Sesack, SR
影响因子：
7.6
作者：
Liu, Zhong-Hua;Shin, Rick;Ikemoto, Satoshi
通讯作者：
Ikemoto, Satoshi
影响因子：
5.5
作者：
Koga, E;Momiyama, T
通讯作者：
Momiyama, T