ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1618929
Age-specific effects of synthetic cannabinoids on cognitive function and hippocampal gene expression in mice: insights from behavioral and molecular correlates
Provisionally accepted
Kaixi Li1Yuanyuan Chen1Yawen Xu1Yuan Pang2
Yongli Bao3Simeng Zhang1Xuesong Shi1Jingzhi Ran1Yanling Qiao1Yizhao Xu4Yiming Wang2Bin Di1
Peng Xu4*- 1China Pharmaceutical University, Nanjing, Jiangsu Province, China
- 2Tsinghua University, Beijing, Beijing, China
- 3Northeast Normal University, Changchun, Jilin Province, China
- 4Key Laboratory of Drug Monitoring and Control, Drug Intelligence and Forensic Center, Ministry of Public Security, China, Beijing, China
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The increasing use of Synthetic cannabinoids (SCs) in adolescents and young adults poses significant medical and psychiatric risks, and previous reports have been dominated by single-age animal studies. Here, we first investigated the effects of a single exposure of the fourth-generation synthetic cannabinoid 4F-ABUTINACA on cognitive behaviors in adolescent (PND 28-35 days) and adult (PND 49-56 days) male mice in an animal model, followed by an age-specific systematic study by conducting a whole-gene transcriptomics study of hippocampal tissue in the brain. Behavioral results showed that 4F-ABUTINACA impaired recognition memory, fear memory extraction, and spatial navigation memory in adolescent mice, as well as spatial navigation memory in adult mice. The transcriptomics results revealed different alterations in age-enriched signaling pathways affected by 4F-ABUTINACA, such as Alzheimer's disease, Parkinson's disease, and neurodegenerative diseases. In addition, 4F-ABUTINACA causes selective down-regulation of transcription of genes involved in stress response and mitochondrial expression in adolescent mice, whereas no significant differences were observed in adult mice. This study provides an innovative resource on the behavioral and molecular landscape of age-specific changes in cognitive function by synthetic cannabinoids and offers new opportunities for follow-up studies to target age-specific functional significance and related molecular mechanisms to be mined.
Keywords: Adolescent, synthetic cannabinoids, Memory, Transcriptomics, 4F-ABUTINACA
Received: 27 Apr 2025; Accepted: 09 Jun 2025.
Copyright: © 2025 Li, Chen, Xu, Pang, Bao, Zhang, Shi, Ran, Qiao, Xu, Wang, Di and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Peng Xu, Key Laboratory of Drug Monitoring and Control, Drug Intelligence and Forensic Center, Ministry of Public Security, China, Beijing, China
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