Transcranial focused ultrasound to nucleus accumbens reverses fentanyl-induced conditioned place preference in rats.

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.