Hrickova Maria, Ruda-Kucerova Jana
Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Prog Neuropsychopharmacol Biol Psychiatry. 2025 Apr 2;138:111355. doi: 10.1016/j.pnpbp.2025.111355. Epub 2025 Apr 3.
Substance addiction is a complex mental disorder with significant unmet treatment needs, especially in terms of effective medications. Craving in addiction is closely linked to the interaction between dopamine and glutamate in the brain's reward pathway. Therefore, drugs targeting glutamatergic signaling may have potential for treatment. This review examines the potential of AMPA/kainate glutamatergic receptor antagonists in reducing addictive-like behaviours in experimental rodents. To this end, the text summarizes the behavioural results of preclinical studies on stimulant substances (cocaine, amphetamine, methamphetamine, MDMA), nicotine, opioids (morphine and heroin), and alcohol. These experiments employ various protocols and routes of administration, using different strains of mice and rats. The main behavioural methods used in the research include behavioural sensitization protocols, drug-induced locomotor activity assessments, conditioned behaviours, and operant self-administration models. The reviewed literature demonstrates the benefit of AMPA/kainate antagonists, mainly in the most studied cocaine dependence, and particularly in attenuating cocaine-seeking behaviour via microinjection into the nucleus accumbens core. Regarding other addictive substances, despite some conflicting results, there is a substantial body of literature showing promising outcomes following systemic or intracerebral administration of AMPA/kainate antagonists. The main issue is the variability of the research protocols used across laboratories, including differences in animal species, strains, sex and environmental conditions. Moreover, each addictive substance exhibits distinct mechanisms of action and addiction development, rendering the pursuit of a universal drug for addiction treatment unrealistic. Nevertheless, AMPA/kainate antagonists seem to have potential as a supportive treatment in addiction to cocaine as well as other substances.
物质成瘾是一种复杂的精神障碍，存在大量未满足的治疗需求，尤其是在有效药物方面。成瘾中的渴望与大脑奖赏通路中多巴胺和谷氨酸之间的相互作用密切相关。因此，针对谷氨酸能信号传导的药物可能具有治疗潜力。本综述探讨了AMPA/海人酸谷氨酸能受体拮抗剂在减少实验啮齿动物成瘾样行为方面的潜力。为此，本文总结了关于兴奋剂（可卡因、苯丙胺、甲基苯丙胺、摇头丸）、尼古丁、阿片类药物（吗啡和海洛因）以及酒精的临床前研究的行为学结果。这些实验采用了各种方案和给药途径，使用了不同品系的小鼠和大鼠。研究中使用的主要行为学方法包括行为敏化方案、药物诱导的运动活动评估、条件性行为和操作性自我给药模型。综述文献表明了AMPA/海人酸拮抗剂的益处，主要体现在对研究最多的可卡因依赖方面，特别是通过向伏隔核核心微量注射来减轻觅可卡因行为。对于其他成瘾物质，尽管有一些相互矛盾的结果，但有大量文献表明，在全身或脑内给予AMPA/海人酸拮抗剂后有良好的结果。主要问题是各实验室使用的研究方案存在差异，包括动物种类、品系、性别和环境条件的不同。此外，每种成瘾物质都表现出独特的作用机制和成瘾发展过程，使得寻求一种通用的成瘾治疗药物不切实际。然而，AMPA/海人酸拮抗剂似乎有潜力作为可卡因及其他物质成瘾的辅助治疗药物。
