The metabotropic glutamate 5 receptor modulates extinction and reinstatement of methamphetamine-seeking in mice.
The metabotropic glutamate 5 receptor modulates extinction and reinstatement of methamphetamine-seeking in mice.
复制标题
DOI：
10.1371/journal.pone.0068371
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lawrence AJ
中科院分区：
文献类型：
--
作者：
Chesworth R;Brown RM;Kim JH;Lawrence AJ
甲基苯丙胺（冰毒）是一种高度成瘾性的精神兴奋剂，没有任何治疗方法可以帮助成瘾者停止使用。谷氨酸能功能障碍与成瘾的发展和维持有关。我们试图评估代谢性谷氨酸5受体（mGlu5）在与冰毒成瘾相关的行为中的作用，因为这种受体与其他药物滥用的行为有关，包括酒精、可卡因和阿片类药物。对mGlu5基因敲除（KO）小鼠进行静脉给药、条件位置偏好和运动致敏试验。自我给药蔗糖用于评估KO小鼠对自然奖励的反应。在mGlu5 KO小鼠中，自我给药的获得和维持，以及自我给药的动机是完整的。重要的是，mGlu5 KO小鼠需要更多的灭绝过程来消除对甲基苯甲胺的操作性反应，并且在暴露于药物相关线索后表现出增强的恢复操作性反应的倾向。当KO小鼠在评估对蔗糖的操作性反应的等效范式中进行测试时，这种表型不存在。KO小鼠条件性位置偏好和运动敏化发育未受影响；然而，先前与药物配对的条件亢进在KO小鼠中升高。这些数据表明，mGlu5在甲基寻求的消失和恢复中发挥作用，并提示mGlu5在调节上下文显著性中发挥作用。
Methamphetamine (METH) is a highly addictive psychostimulant with no therapeutics registered to assist addicts in discontinuing use. Glutamatergic dysfunction has been implicated in the development and maintenance of addiction. We sought to assess the involvement of the metabotropic glutamate 5 receptor (mGlu5) in behaviours relevant to METH addiction because this receptor has been implicated in the actions of other drugs of abuse, including alcohol, cocaine and opiates. mGlu5 knockout (KO) mice were tested in intravenous self-administration, conditioned place preference and locomotor sensitization. Self-administration of sucrose was used to assess the response of KO mice to a natural reward. Acquisition and maintenance of self-administration, as well as the motivation to self-administer METH was intact in mGlu5 KO mice. Importantly, mGlu5 KO mice required more extinction sessions to extinguish the operant response for METH, and exhibited an enhanced propensity to reinstate operant responding following exposure to drug-associated cues. This phenotype was not present when KO mice were tested in an equivalent paradigm assessing operant responding for sucrose. Development of conditioned place preference and locomotor sensitization were intact in KO mice; however, conditioned hyperactivity to the context previously paired with drug was elevated in KO mice. These data demonstrate a role for mGlu5 in the extinction and reinstatement of METH-seeking, and suggests a role for mGlu5 in regulating contextual salience.
登录
查看更多内容
影响因子：
3.6
作者：
Christensen, Chesley J.;Silberberg, Alan;Hursh, Steven R.;Roma, Peter G.;Riley, Anthony L.
通讯作者：
Riley, Anthony L.
影响因子：
2.3
作者：
Ben-Shahar, Osnat;Obara, Ilona;Ary, Alexis W.;Ma, Natalie;Mangiardi, Mario A.;Medina, Robert L.;Szumlinski, Karen K.
通讯作者：
Szumlinski, Karen K.
影响因子：
3.4
作者：
Aoki, T;Narita, M;Suzuki, T
通讯作者：
Suzuki, T
DOI：
10.1196/annals.1441.015
发表时间：
2008-01-01
期刊：
ADDICTION REVIEWS 2008
影响因子：
--
作者：
Carroll, F. Ivy
通讯作者：
Carroll, F. Ivy
影响因子：
25
作者：
Baker, DA;McFarland, K;Kalivas, PW
通讯作者：
Kalivas, PW