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Effect of low-intensity focused ultrasound on hippocampus of alcohol addicted mice: a preliminary study

Qian Wang, Xiaoqing Xiang, Lianjie Peng, Chunxia Liang, Qiong Li, Shuang Liang, Jianzhong Zou, Yanlin Chen

Frontiers in Neuroscience 2026 · 10.3389/fnins.2026.1789927

rodentsubstance use disorderbehaviourhistology molecular

Abstract

Alcohol addiction is a chronic relapsing brain disorder characterized by significant neurobiological changes, particularly within the hippocampus, which mediates emotional regulation and reward-seeking behavior. Previous studies have shown that alcohol-induced neuronal injury contributes to withdrawal-associated anxiety and persistent alcohol preference. This study investigated the therapeutic effects of low-intensity focused ultrasound (LIFU) on the hippocampus in a mouse model of alcohol addiction. Twenty-six male C57BL/6 mice were allocated to an alcohol-exposed group ( n = 20) and a control group ( n = 6). Following a 28-day modeling period, the alcohol group was randomly subdivided into a therapy group and a sham group. The therapy group received LIFU treatment, while the sham group underwent an identical procedure with the ultrasound transducer powered off. After seven days of treatment, the therapy group exhibited less severe anxiety symptoms upon alcohol withdrawal and a reduced preference for alcohol compared to the sham group. The brain-derived neurotrophic factor (BDNF) concentration was significantly lower in the therapy group than in the sham group, but did not differ significantly from the control group. Hippocampal HE staining revealed more pronounced degeneration and apoptosis of granule cells in the dentate gyrus (DG) region in the sham group relative to the therapy group. These preliminary findings suggest that LIFU may modulate alcohol addiction by mitigating hippocampal neuronal injury.

Abstract via europepmc.

Speciesmouse (C57BL/6)
Subjects10, 3, 3, 3swept animals
Sessions per subject7
Randomisedyes
Blindingnot reported
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingoffline
Anaesthesiaanaesthetised
Readoutsbehaviour, histology molecular — alcohol preference test; open field; forced swim; elevated plus maze; hippocampal BDNF ELISA; HE staining
Direction of effectmixed or unclearAfter 7 days of hippocampal LIFU, alcohol-addicted mice showed lower alcohol preference and less anxiety-like behaviour than sham, lower hippocampal BDNF than sham (which had a surge, near control) and fewer apoptotic dentate granule cells; no neural activity was measured.
Adverse eventsnot reportedOne sham-group mouse died of natural causes during treatment; no other safety assessment described.

Exposures

Exposure 1: LIFU over hippocampal projection area (7 daily sessions)

Target: hippocampus — “hippocampal projection area on the skull”
Device: other named manufacturer · Chongqing Haifu Medical Technology Co., Ltd. · Model-CZG Ultrasound Therapeutic Device for Arthritis ✓

Pulse timing
Waveformnot reported
Fundamental frequency (kHz)600✓✓✓
Pulse duration (ms)not reported
Pulse repetition frequency (Hz)not reported
Duty cycle (%)not reported
Sonication duration (s)300, 600, 900swept✓✓✓⚑
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Ispta, domain unspecified (W/cm²)0.6✓✓✓⚑
Protocol, in the paper’s words

Daily irradiation for 0, 5, 10 or 15 min over 7 consecutive days in the duration-selection experiment (normal mice); 15 min/d for 7 consecutive days was then used in the alcohol model. Pulsing is not described. Mice anaesthetised with isoflurane; 2 cm probe over the hippocampal projection area.

Flags from extraction

  • exposures[0].unspecified_domain.ispta_w_cm2 — Paper gives 'power 0.6 W/cm2 +/- 20%' for a physiotherapy device without naming the intensity metric or the domain; placed in ispta as the nearest field.
  • n_subjects — 38 mice were obtained: 26 in the addiction model (6 control, 20 alcohol; 9 sham, 9 therapy analysed) and 12 normal mice for duration selection (3 per duration group, including 0 min). Not all were sonicated.
  • exposures[0].timing.sonication_duration_s — List is the 5, 10 and 15 min durations tested in normal mice (0 min is no exposure); the alcohol model used 15 min.
  • exposures[0].device — Arthritis physiotherapy device with a stated focal plane distance; focusing and waveform not described.
  • direction_of_effect — Aim was protective / disease-modifying; no activity readout, direction not clear.