Work

Anxiety-like behaviors induced by chronic administration of the synthetic cannabinoid 4F-ABUTINACA in rats and the underlying mechanisms

Year: 2026

Type: article

Abstract: OBJECTIVES: -tetrahydrocannabinol (THC)-like discrimina-tive stimulus effects of 4F-ABUTINACA and to investigate the potential mechanisms underlying anxiety-like behaviors induced by chronic 4F-ABUTINACA administration. METHODS: =16 per group): vehicle control group, 4F-ABUTINACA low-dose group (0.3 mg/kg), and 4F-ABUTINACA high-dose group (2.0 mg/kg). All rats received intraperitoneal injections of vehicle or 4F-ABUTINACA for 15 consecutive days. Anxiety-like behaviors were assessed using the open field test (OFT) and elevated plus maze (EPM) test on day 21 (short-term withdrawal) and day 40 (long-term withdrawal). Immunofluorescence staining was used to examine glial cell activation and changes in inhibitory synaptic markers in the hippocampus. Western blotting was performed to detect the expression of synaptic plasticity-related proteins in the rat hippocampus. RESULTS: -aspartate receptor (NMDAR) 2A and NMDAR2B levels, increased glutamate receptor ionotropic AMPA type subunit 1 (GluA1) levels in both groups, as well as decreased synaptosome-associated protein 25 (SNAP25) levels in the low-dose group], and inhibitory synaptic damage [decreased gephyrin levels, with decreased vesicular GABA transporter (VGAT) levels also observed in the high-dose group], with some changes being more pronounced in the high-dose group. At long-term withdrawal, the neuroinflammatory indicators in the low-dose 4F-ABUTINACA group had largely recovered, whereas neuroinflammation persisted in the high-dose group (IBA-1-positive cell counts and GFAP expression remained elevated), accompanied by more extensive synaptic damage (decreased NMDAR2A, NMDAR2B, and SNAP25 levels) and inhibitory synaptic damage. CONCLUSIONS: 4F-ABUTINACA produces THC-like discriminative stimulus effects via CB1 receptor activation, suggesting that it has abuse liability. Chronic 4F-ABUTINACA administration induces anxiety-like behaviors in rats, and the underlying mechanism may involve sustained upregulation of microglial and astrocytic markers and impaired synaptic plasticity in the hippocampus.

Source: Journal of Zhejiang University (Medical Sciences)

DOI: 10.3724/zdxbyxb-2025-0891

Authors: Baobao SHI, Haitao WANG, Wenhua ZHOU, Miaojun LAI

Institutions: North China University of Science and Technology, Ningbo University, Ningbo Kangning Hospital

Language: Chinese

Topic: Cannabis and Cannabinoid Research

Subfield: Pharmacology (medical)

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

Funder: National Natural Science Foundation of China