Department of Psychology, Arizona State University, PO Box 871104, 950 S McAllister Avenue, Tempe, AZ 85287, USA.
Psychopharmacology (Berl). 2013 Jan;225(1):151-9. doi: 10.1007/s00213-012-2804-z. Epub 2012 Jul 21.
Methamphetamine (METH) is a highly potent and addictive psychostimulant with severe detrimental effects to the health of users. Currently, METH addiction is treated with a combination of cognitive and behavioral therapies, but these traditional approaches suffer from high relapse rates. Furthermore, there are currently no pharmacological treatment interventions approved by the FDA specifically for the treatment of METH addiction.
Metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulators (NAMs) have shown promise in significantly attenuating drug self-administration and drug-seeking in reinstatement paradigms. However, studies assessing the potential efficacy of mGluR5 NAMs that have been tested in human subjects are lacking. The current study sought to assess the effect of the mGluR5 NAM fenobam on METH-seeking behavior.
Rats were trained to self-administer METH (0.05 mg/kg i.v.), and following extinction, tested for effects of fenobam (5, 10, or 15 mg/kg intraperitoneal) on cue- and drug-induced reinstatement of METH-seeking. To determine if fenobam also alters reinstatement of seeking of natural reinforcers, separate groups of rats were trained to self-administer sucrose or food pellets and were tested for the effects of fenobam on cue-induced reinstatement of sucrose- and food-seeking.
Fenobam attenuated drug- and cue-induced reinstatement of METH-seeking behavior at doses of 10 and 15 mg/kg. Fenobam also attenuated cue-induced reinstatement of sucrose- and food-seeking at all doses tested.
The mGluR5 NAM fenobam attenuates the reinstatement of METH-seeking behavior, but these effects may be due to nonspecific suppression of general appetitive behaviors.
甲基苯丙胺（METH）是一种效力高且成瘾性强的精神兴奋剂，会对使用者的健康造成严重的不良影响。目前，METH 成瘾的治疗方法是结合认知和行为疗法，但这些传统方法的复发率很高。此外，目前还没有美国食品和药物管理局（FDA）批准的专门用于治疗 METH 成瘾的药物治疗干预措施。
代谢型谷氨酸受体 5（mGluR5）负变构调节剂（NAM）在显著减轻药物自我给药和药物寻求的复吸模式中显示出有希望的效果。然而，缺乏在人体受试者中测试的 mGluR5 NAM 的潜在疗效评估研究。本研究旨在评估 mGluR5 NAM 非布司他对 METH 寻求行为的影响。
大鼠接受 METH（0.05mg/kg 静脉注射）的自我给药训练，在消退后，测试非布司他（5、10 或 15mg/kg 腹腔内给药）对线索和药物诱导的 METH 寻求复吸的影响。为了确定非布司他是否也改变了对自然强化物寻求的复吸，分别训练一组大鼠自我给予蔗糖或食物丸，并测试非布司他对蔗糖和食物寻求的线索诱导复吸的影响。
非布司他在 10 和 15mg/kg 剂量下减弱了药物和线索诱导的 METH 寻求复吸。非布司他还在所有测试剂量下减弱了线索诱导的蔗糖和食物寻求复吸。
mGluR5 NAM 非布司他减弱了 METH 寻求行为的复吸，但这些作用可能是由于对一般食欲行为的非特异性抑制。
