Transcranial focused ultrasound to nucleus accumbens reverses fentanyl-induced conditioned place preference in rats
Seung-Schik Yoo, Madeline S. Ewell, Evan C. Smith, Isabel L. Yu, Hyun-Chul Kim, Rajeev I. Desai
PLOS One 2025 · 10.1371/journal.pone.0329748
Abstract
Fentanyl-related opioid use disorder (OUD) continues to be a substantial public health concern. Current pharmacological treatments, using methadone and buprenorphine, can cause adverse side effects, and patients often relapse, necessitating alternative treatment strategies. Transcranial focused ultrasound (tFUS), a noninvasive neuromodulation technique with deep brain penetrability and high spatial selectivity, is emerging as a potential intervention for treatment of OUD. To evaluate utility of tFUS in modulating the function of reward circuitry, we applied functionally suppressive tFUS to the nucleus accumbens (nAcc) of male rats to determine if it attenuated fentanyl-induced conditioned place preference (CPP). Fentanyl CPP scores were significantly attenuated following tFUS administration to the nAcc, suggesting tFUS application weakens the rewarding effects of fentanyl in rats. Physiological, behavioral, and neuropathological endpoints were unaffected by tFUS, confirming that other factors did not contribute to the observed effects. Taken together, these results support the use of tFUS as a potential treatment strategy of OUD by non-invasively modulating activity in key reward-related brain regions implicated in OUD.
Abstract via europepmc.
Exposures
Exposure 1: tFUS to nucleus accumbens, 30 min
Target: nucleus accumbens — “nucleus accumbens (nAcc)”
Device: custom-built · in-house · single-element 600 kHz PZT transducer with polyetherimide acoustic lens ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 600 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 5% | ✓✓✓ |
| Sonication duration (s) | 1,800 | ✓✓✓⚑ |
| 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) | 380 | ✓✓✓⚑ |
| Isppa, domain unspecified (W/cm²) | 5 | ✓✓✓ |
| Ispta, domain unspecified (W/cm²) | 0.25 | ✓✓✓⚑ |
0.5 ms pulse duration at 100 Hz PRF at 5 W/cm2 Isppa, delivered to the nAcc for 30 min under isoflurane anaesthesia; verum and sham sessions in randomised order about 2 h apart on day 5 after 4 days of fentanyl conditioning.
Flags from extraction
exposures[0].timing.sonication_duration_s— Duration given as 30 min of delivery; the within-session on/off structure of the 30 min is not stated beyond the pulse parameters, so 1800 s is recorded as stated duration of delivery.exposures[0].unspecified_domain.pressure_kpa— Pressure 0.38 MPa and Isppa 5 W/cm2 are not explicitly assigned to water or brain; field was mapped in degassed water but the sentence does not say the values are free-field.exposures[0].unspecified_domain.ispta_w_cm2— Paper gives 250 mW/cm2; converted to W/cm2 only.n_sessions_per_subject— Verum and sham interventions were both given on day 5 about 2 h apart; recorded as 2 interventions per animal.blinding— Only the video raters are stated to be blinded to the sequence; treatment was not blinded to the operator.