Department of Toxicology, Faculty of Pharmacy, Jagiellonian University, Medical College, Kraków, Poland.
Institute of Pharmacology Polish Academy of Sciences, Department of Drug Addiction Pharmacology, Kraków, Poland.
Pharmacol Rep. 2017 Oct;69(5):1073-1081. doi: 10.1016/j.pharep.2017.04.016. Epub 2017 Apr 27.
In the cocaine addiction the development from transient into persistent neuroplastic changes strongly involves the glutamatergic system. In this respect, among glutamatergic receptors special attention is paid to the group II of metabotropic glutamatergic receptors (mGlu2/3R) which are involved in the transition from drug use to drug addiction including the relapse mechanisms.
The present study employed radioligand binding and Western blot assays to study mGlu2/3R density, affinity and protein expression in selected rat brain areas after cocaine self-administration, extinction training and cocaine-induced reinstatement. Rats were randomly assigned in triads to one of three conditions: contingent cocaine intravenous self-administration, non-contingent injections of cocaine (yoked cocaine), or saline yoked to the intake of the self-administering subject.
Cocaine self-administration and yoked cocaine delivery resulted in a significant increase in the mGlu2/3R density in the prefrontal cortex and the dorsal striatum, while 10-day extinction training provoked a reduction in the prefrontal cortex and the nucleus accumbens. Cocaine abstinence also enhanced an increase in the [H]ligand binding to mGlu2/3R in the prefrontal cortex. During reinstatement the cocaine challenge dose (10mg/kg, ip) led to important elevation in the mGlu2/3R density in the prefrontal cortex.
Our study demonstrated the role of mGlu2/3R localized in the prefrontal cortex-striatum pathways to cocaine repeated exposure.
在可卡因成瘾中，从短暂到持久的神经可塑性变化的发展强烈涉及谷氨酸能系统。在这方面，在谷氨酸能受体中，特别关注代谢型谷氨酸能受体（mGlu2/3R）的第二组，它们参与从药物使用到药物成瘾的转变，包括复发机制。
本研究采用放射性配体结合和 Western blot 分析，研究可卡因自我给药、消退训练和可卡因诱导复吸后，选定大鼠脑区的 mGlu2/3R 密度、亲和力和蛋白表达。大鼠随机分为三组，分别接受以下三种处理之一：条件性可卡因静脉自我给药、非条件性可卡因注射（偶联可卡因）或盐水偶联到自我给药动物的摄入。
可卡因自我给药和偶联可卡因给药导致前额叶皮层和背侧纹状体的 mGlu2/3R 密度显著增加，而 10 天的消退训练导致前额叶皮层和伏隔核的 mGlu2/3R 密度降低。可卡因戒断也增强了前额叶皮层中[H]配体与 mGlu2/3R 的结合增加。在复吸期间，可卡因挑战剂量（10mg/kg，ip）导致前额叶皮层中 mGlu2/3R 密度的重要升高。
我们的研究表明，位于前额叶皮层-纹状体通路的 mGlu2/3R 参与了可卡因的重复暴露。
