Attenuation of methamphetamine seeking by the mGluR2/3 agonist LY379268 in rats with histories of restricted and escalated self-administration.
Attenuation of methamphetamine seeking by the mGluR2/3 agonist LY379268 in rats with histories of restricted and escalated self-administration.
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DOI：
10.1016/j.neuropharm.2012.05.037
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发表时间：
2013-03
影响因子：
4.7
通讯作者：
Olive MF
中科院分区：
文献类型：
--
作者：
Kufahl PR;Watterson LR;Nemirovsky NE;Hood LE;Villa A;Halstengard C;Zautra N;Olive MF
最近的研究结果表明，II组代谢型谷氨酸受体（mGluR 2/3）在精神兴奋剂的强化作用，并已确定这些受体作为药物成瘾的潜在治疗靶点。在这里，我们研究了mGluR 2/3刺激的影响，提示和药物引发的恢复在大鼠与不同的历史甲基苯丙胺（METH）自我管理的培训，在两种条件下：16个日常会议的短期访问（90分钟/天，ShA），或8个日常会议的短期访问，然后由8个会议的长期访问（6小时/天，LGA）。在自我给药和随后的消退训练之后，用选择性mGluR 2/3激动剂LY 379268（可变剂量，0 - 3 mg/kg）预处理大鼠，暴露于METH配对线索或启动注射METH（1 mg/kg），并测试寻求METH行为的恢复。LGA大鼠在训练的后半部分自我施用更大量的METH，但是当用载体预处理时，ShA和LGA大鼠以相等的响应率显示出线索和药物引发的恢复。然而，LgA大鼠表现出对mGluR 2/3刺激的更大敏感性，在0.3 mg/kg和更高剂量的LY 379268后的线索诱导的恢复期间具有减弱的反应，而ShA大鼠在1.0 mg/kg和3.0 mg/kg LY 379268后减少线索诱导的恢复行为。此外，在0.3 mg/kg和更高剂量的LY 379268后，LgA和ShA大鼠均表现出降低的MET引发的恢复行为。另一组对照大鼠接受自我给药蔗糖丸的训练，并在1.0和3.0 mg/kg LY 379268后表现出减弱的线索诱导的蔗糖寻求行为。总之，结果表明，LY 379268对具有不同METH摄入史的大鼠的线索诱导的恢复行为具有不同的衰减作用。
Recent findings implicate group II metabotropic glutamate receptors (mGluR2/3) in the reinforcing effects of psychostimulants and have identified these receptors as potential treatment targets for drug addiction. Here, we investigated the effects of mGluR2/3 stimulation on cue- and drug-primed reinstatement in rats with different histories of methamphetamine (METH) self-administration training, under two conditions: 16 daily sessions of short access (90 min/day, ShA), or 8 daily sessions of short access followed by 8 sessions of long access (6 hr/day, LgA). Following self-administration and subsequent extinction training, rats were pretreated with the selective mGluR2/3 agonist LY379268 (variable dose, 0 – 3 mg/kg), exposed to METH-paired cues or a priming injection of METH (1 mg/kg), and tested for reinstatement of METH-seeking behavior. LgA rats self-administered greater amounts of METH during the second half of training, but when pretreated with vehicle, ShA and LgA rats showed cue- and drug-primed reinstatement at equivalent response rates. However, LgA rats demonstrated greater sensitivity to mGluR2/3 stimulation with attenuated responding during cue-induced reinstatement after 0.3 mg/kg and higher doses of LY379268, whereas ShA rats decreased cue-induced reinstatement behavior following 1.0 mg/kg and 3.0 mg/kg LY379268. Additionally, both LgA and ShA rats exhibited decreased METH-primed reinstatement behavior following 0.3 mg/kg and higher doses of LY379268. A separate group of control rats was trained to self-administer sucrose pellets, and demonstrated attenuated cue-induced sucrose-seeking behavior following 1.0 and 3.0 mg/kg LY379268. Together, the results indicate that LY379268 has differential attenuating effects on cue-induced reinstatement behavior in rats with different histories of METH intake.
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影响因子：
7.3
作者：
Dhanya RP;Sidique S;Sheffler DJ;Nickols HH;Herath A;Yang L;Dahl R;Ardecky R;Semenova S;Markou A;Conn PJ;Cosford ND
通讯作者：
Cosford ND
影响因子：
5.3
作者：
Baptista, MAS;Martin-Fardon, R;Weiss, F
通讯作者：
Weiss, F
DOI：
10.1037/0278-7393.31.2.238
发表时间：
2005-03-01
影响因子：
2.6
作者：
Beckers, T;De Houwer, J;Miller, RR
通讯作者：
Miller, RR
影响因子：
5
作者：
Bäckström, P;Hyytiä, P
通讯作者：
Hyytiä, P
影响因子：
25
作者：
Ahmed, SH;Kenny, PJ;Markou, A
通讯作者：
Markou, A