The elucidation of synaptic density changes provides valuable insights into the underlying brain mechanisms of substance use. In preclinical studies, synaptic density markers, like spine density, are altered by substances of abuse (e.g., alcohol, amphetamine, cannabis, cocaine, opioids, nicotine). These changes could be linked to phenomena including behavioral sensitization and drug self-administration in rodents. However, studies have produced heterogeneous results for spine density across substances and brain regions. Identifying patterns will inform translational studies given tools that now exist to measure in vivo synaptic density in humans. We performed a meta-analysis of preclinical studies to identify consistent findings across studies. PubMed, ScienceDirect, Scopus, and EBSCO were searched between September 2022 and September 2023, based on a protocol (PROSPERO: CRD42022354006). We screened 6083 publications and included 70 for meta-analysis. The meta-analysis revealed drug-specific patterns in spine density changes. Hippocampal spine density increased after amphetamine. Amphetamine, cocaine, and nicotine increased spine density in the nucleus accumbens. Alcohol and amphetamine increased, and cannabis reduced, spine density in the prefrontal cortex. There was no convergence of findings for morphine’s effects. The effects of cocaine on the prefrontal cortex presented contrasting results compared to human studies, warranting further investigation. Publication bias was small for alcohol or morphine and substantial for the other substances. Heterogeneity was moderate-to-high across all substances. Nonetheless, these findings inform current translational efforts examining spine density in humans with substance use disorders.

突触密度变化的阐明为了解物质使用的潜在大脑机制提供了有价值的见解。在临床前研究中，突触密度标记（如脊柱密度）会因滥用物质（例如酒精、安非他明、大麻、可卡因、阿片类药物、尼古丁）而改变。这些变化可能与啮齿类动物的行为敏感性和药物自我给药等现象有关。然而，研究对不同物质和大脑区域的脊柱密度产生了异质性结果。鉴于目前存在用于测量人类体内突触密度的工具，识别模式将为转化研究提供信息。我们对临床前研究进行了荟萃分析，以确定跨研究的一致结果。根据协议（PROSPERO：CRD42022354006），在 2022 年 9 月至 2023 年 9 月期间对 PubMed、ScienceDirect、Scopus 和 EBSCO 进行了检索。我们筛选了 6083 篇出版物，其中 70 篇进行了荟萃分析。荟萃分析揭示了脊柱密度变化的药物特异性模式。安非他明后海马棘密度增加。安非他明、可卡因和尼古丁增加了伏隔核的棘密度。酒精和安非他明增加了前额皮质的棘密度，而大麻则减少了。关于吗啡的作用，目前还没有一致的研究结果。与人类研究相比，可卡因对前额皮质的影响呈现出截然不同的结果，值得进一步研究。酒精或吗啡的发表偏倚较小，而其他物质的发表偏倚较大。所有物质的异质性为中度至高度。尽管如此，这些发现为目前检查患有物质使用障碍的人类脊柱密度的转化工作提供了信息。