Neuromodulation with stereotactic radiosurgery to the nucleus accumbens in a rodent model of opioid use disorder

Opioid use disorder remains a health crisis with high risk of relapse and mortality, and new therapeutic options beyond the current standard of care are needed. Here, we present results from a pilot cohort of an opioid use disorder rodent model undergoing neuromodulation with stereotactic radiosurgery. Eight rats were made opioid dependent via daily intraperitoneal morphine injections. Serial 18 F-FDG PET/CT imaging revealed decreased metabolism in the striatum after opioid dependence was established. Four rats were treated with stereotactic radiosurgery (SRS) with a dose of 40 Gy targeting the bilateral nucleus accumbens, and four rats remained unirradiated. Post-SRS 18 F-FDG PET/CT showed a reversal of striatal metabolic activity in SRS-treated rats compared to the unirradiated group. Replicated behavioral assessments with naltrexone-precipitated withdrawal challenges at six weeks after SRS treatment demonstrated reduced opioid dependence in SRS-treated rats versus unirradiated rats, with SRS-treated rats performing comparably to morphine-naïve controls. These results were observed without gross blunting of behaviors or overt adverse health effects in the SRS-treated group. These preliminary findings from this pilot cohort are hypothesis-generating and offer encouragement for further investigation of stereotactic radiosurgery as a non-invasive approach for neuromodulation of the dysregulated reward circuitry in opioid use disorder.