Department of Psychology, Arizona State University, PO Box 871104, Tempe, AZ 85287-1104, USA.
Neuropharmacology. 2013 Mar;66:290-301. doi: 10.1016/j.neuropharm.2012.05.037. Epub 2012 May 31.
Recent findings implicate group II metabotropic glutamate receptors (mGluR(2/3)) in the reinforcing effects of psychostimulants and have identified these receptors as potential treatment targets for drug addiction. Here, we investigated the effects of mGluR(2/3) 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 h/day, LgA). Following self-administration and subsequent extinction training, rats were pretreated with the selective mGluR(2/3) 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 mGluR(2/3) 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. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'.
最近的研究结果表明，II 型代谢型谷氨酸受体（mGluR(2/3)）参与了精神兴奋剂的强化作用，并将这些受体鉴定为药物成瘾的潜在治疗靶点。在这里，我们研究了 mGluR(2/3)刺激对不同甲基苯丙胺（METH）自我给药训练史的大鼠线索和药物引发复吸的影响，在两种情况下进行：16 个每日短时间接触（90 分钟/天，ShA），或 8 个每日短时间接触后 8 个长时间接触（6 小时/天，LgA）。在自我给药和随后的消退训练后，大鼠预先用选择性 mGluR(2/3)激动剂 LY379268（可变剂量，0-3 mg/kg）预处理，暴露于 METH 配对线索或 METH 引发注射（1 mg/kg），并测试 METH 寻求行为的复吸。LgA 大鼠在训练的后半段自我给药量更大，但当用载体预处理时，ShA 和 LgA 大鼠在同等反应率下显示线索和药物引发的复吸。然而，LgA 大鼠在 0.3 mg/kg 和更高剂量的 LY379268 后，在线索诱导的复吸中表现出对 mGluR(2/3)刺激的敏感性降低，而 ShA 大鼠在 1.0 mg/kg 和 3.0 mg/kg LY379268 后，线索诱导的复吸行为减少。此外，LgA 和 ShA 大鼠在 0.3 mg/kg 和更高剂量的 LY379268 后，METH 引发的复吸行为减少。另一组对照大鼠被训练自我给予蔗糖丸，并在 1.0 和 3.0 mg/kg LY379268 后表现出减弱的线索诱导的蔗糖寻求行为。总之，这些结果表明，LY379268 对不同 METH 摄入史大鼠的线索诱导复吸行为具有不同的减弱作用。本文是特刊“代谢型谷氨酸受体”的一部分。
