Comparison of dopamine D1 and D5 receptor knockout mice for cocaine locomotor sensitization.
Comparison of dopamine D1 and D5 receptor knockout mice for cocaine locomotor sensitization.
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多巴胺D1和D5受体基因敲除小鼠可卡因运动敏化的比较。
DOI：
10.1007/s00213-008-1165-0
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发表时间：
2008-09
影响因子：
3.4
通讯作者：
Holmes, Andrew
中科院分区：
文献类型：
--
作者：
Karlsson, Rose-Marie;Hefner, Kathryn R.;Sibley, David R.;Holmes, Andrew
关键词：
有令人信服的证据支持多巴胺和D1R样（D1R, D5R）受体亚家族对滥用精神兴奋剂药物的行为和神经效应的贡献。D1R和D5R亚型在介导这些效应中的相对作用尚不清楚。直接比较（C57BL/6J） D1R基因敲除（KO）和D5R基因敲除（KO）小鼠的基线运动探索、可卡因急性运动反应和重复给药后的运动致敏性。目的探讨可卡因条件位置偏好（CPP）在D5R KO中的作用。研究人员评估了D1R KO、D5R KO和野生型（WT）小鼠的基线野外探索、15 mg/kg急性可卡因对运动的刺激作用，以及在20或30 mg/kg可卡因的家庭笼中反复给药后对可卡因的致敏运动反应。D5R KO和WT对15 mg/kg可卡因进行CPP检测。与WT相比，D1R KO表现出适度的基础亢进和中心探索增加。可卡因的急性运动反应在D1R KO中一直不存在，而在D5R KO中则完整。D5R KO对可卡因的运动敏化正常，CPP正常。D1R KO对30 mg/kg可卡因没有表现出致敏性运动反应。D1R型KO的致敏失败不是由于过度的刻板印象。令人惊讶的是，D1R KO显示出对20毫克/公斤可卡因适度致敏的证据。D5R KO不会改变对可卡因或可卡因CPP的急性或致敏性运动反应。D5R KO可消除对可卡因的急性运动反应，但在所有剂量下都不能完全阻止对可卡因的运动致敏。
There is compelling support for the contribution of dopamine and the D1R-like (D1R, D5R) receptor subfamily to the behavioral and neural effects of psychostimulant drugs of abuse. The relative roles of D1R and D5R subtypes in mediating these effects are not clear. To directly compare (C57BL/6J congenic) D1R knockout (KO) and D5R KO mice for baseline locomotor exploration, acute locomotor responses to cocaine, and locomotor sensitization to repeated cocaine administration. To examine cocaine conditioned place preference (CPP) in D5R KO. D1R KO, D5R KO and wild-type (WT) were assessed for baseline open field exploration, locomotor-stimulating effects of 15 mg/kg acute cocaine, and sensitized locomotor responses to cocaine following repeated home cage treatment with 20 or 30 mg/kg cocaine. D5R KO and WT were tested for CPP to 15 mg/kg cocaine. D1R KO showed modest basal hyperactivity and increased center exploration relative to WT. Acute locomotor responses to cocaine were consistently absent in D1R KO, but intact in D5R KO. D5R KO showed normal locomotor sensitization to cocaine, and normal cocaine CPP. D1R KO failed to show a sensitized locomotor response to 30 mg/kg cocaine. Failure to sensitize in D1R KO was not due to excessive stereotypies. Surprisingly, D1R KO showed evidence of modest sensitization to 20 mg/kg cocaine. D5R KO does not alter acute or sensitized locomotor responses to cocaine, or cocaine CPP. D5R KO abolishes acute locomotor response to cocaine, but does not fully prevent locomotor sensitization to cocaine at all doses.
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影响因子：
3.4
作者：
Elliot, EE;Sibley, DR;Katz, JL
通讯作者：
Katz, JL
影响因子：
2.9
作者：
CERVO, L;SAMANIN, R
通讯作者：
SAMANIN, R
影响因子：
5.3
作者：
Heusner, CL;Palmiter, RD
通讯作者：
Palmiter, RD
影响因子：
3.4
作者：
Boyce-Rustay, Janel M.;Holmes, Andrew
通讯作者：
Holmes, Andrew
影响因子：
5.3
作者：
Centonze, D;Grande, C;Calabresi, P
通讯作者：
Calabresi, P