MR-Guided Focused Ultrasound Neuromodulation of Nucleus Accumbens to Attenuate Oral Fentanyl Motivation in A Self-Administration Rat Model
David A Martin, Abubakr Eldirdiri, Thomas Ernst, Eric Cunningham, Segun Bernard, Sandesh Kamdi, Donna J Calu, Linda Chang
2026 · 10.64898/2026.10.17.759605
Abstract
Introduction: Transcranial low-intensity focused ultrasound (LIFU) is being explored as a non-invasive approach for neuromodulation to treat opioid use disorder (OUD). Methods: We evaluated MR-guided focused ultrasound, with LIFU, targeting nucleus accumbens (MRgLIFU-NAc) bilaterally, using MR-acoustic radiation force-imaging (MR-ARFI) to ensure accurate targeting and adjust for FUS intensity delivered at the target. Male and female rats were trained to self-administer fentanyl/sucrose (70ug/ml fentanyl citrate in 5% sucrose) or 5% sucrose alone. Three cohorts of rats (total n=76) were evaluated on progressive ratio (PR) responding for oral fentanyl/sucrose at either 4 or 24 hours post-MRgLIFU-NAc. Animals in the first two cohorts received repeated rounds of LIFU or sham (anesthesia-duration matched). In cohort 3, we used a counterbalanced within-subjects design in which rats received both LIFU and sham one week apart. Results: Reducing sucrose concentrations decreased responding for sucrose alone more than for fentanyl/sucrose, demonstrating a role for fentanyl in the reinforcing properties of fentanyl/sucrose. Across three sonication schemes, MRgLIFU-NAc did not attenuate PR performance for oral fentanyl/sucrose at 4 or 24-hours post-LIFU relative to controls. Adjusting LIFU intensity with MR-ARFI did not correlate with changes in PR from baseline. We confirmed that NAc is the correct target by bilateral inactivation of NAc with muscimol/baclofen mixture (50 + 50 ng/side), which reduced PR responding for fentanyl/sucrose. Conclusion: The three sets of LIFU parameters, with repeated MRgLIFU-NAc sessions, did not produce detectable changes in oral fentanyl/sucrose motivation. Further studies are required to determine effective LIFU parameters needed to reduce NAc-dependent fentanyl motivation.
Abstract via europepmc.
Exposures
Exposure 1: MRgLIFU to bilateral NAc, Schemes 1-3
Target: nucleus accumbens — “nucleus accumbens (NAc), bilateral”
Device: IGT / Imasonic · Image Guided Therapy (IGT), Pessac, France · MR-compatible 1.5 MHz FUS system, 8-element annular array ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,500 | ✓✓✓ |
| Pulse duration (ms) | 5, 300swept | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 100, 1swept | ✓✓✓ |
| Duty cycle (%) | 50, 30swept | ✓✓✓ |
| Sonication duration (s) | 900, 600, 1,200swept | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported | |
| Pressure, domain unspecified (kPa) | 2,000, 900swept | ✓✓✓⚑ |
| Ispta, domain unspecified (W/cm²) | 6.3, 7.6swept | ✓✓✓⚑ |
Scheme 1: 500 ms bursts repeated every 5000 ms, containing 5 ms pulses at 100 Hz, for 15 min at 2.0 MPa. Schemes 2 and 3: 300 ms pulses at 1 Hz (30% duty cycle) with no burst structure, for 10 or 20 min at 0.9 MPa. Repeated rounds, up to three per rat, one week or more apart.
Flags from extraction
exposures[0].timing.pulse_duration_ms— List is [Scheme 1, Schemes 2 and 3]; Scheme 1 is nested (5 ms pulses at 100 Hz inside 500 ms bursts every 5 s), so the 5% duty cycle is overall; the Discussion calls it 50% duty within bursts.exposures[0].unspecified_domain.pressure_kpa— Table lists 'Acoustic Pressure' 2.0 and 0.9 MPa (text: 'target acoustic pressure'); domain not stated. Converted from MPa.exposures[0].timing.sonication_duration_s— Order Scheme 1 (15 min), Scheme 2 (10 min), Scheme 3 (20 min), converted from minutes.sham_type— Sham was anesthesia-only (duration matched), no transducer procedure described.exposures[0].unspecified_domain.ispta_w_cm2— Order Scheme 1, Schemes 2 and 3; table typography garbled.n_subjects— N=76 across three cohorts, of which a subset (N=14) also received muscimol/baclofen cannula work; some rats excluded for training failure.