UC San Diego

Nicotine dependence represents a significant public health concern, often characterized by withdrawal symptoms that complicate cessation efforts and contribute to relapse. This study rigorously investigates the therapeutic efficacy of Deep Brain Stimulation (DBS) targeting the nucleus accumbens shell (NAc shell) in alleviating withdrawal symptoms associated with nicotine vapor exposure in a rat model. Nicotine dependence was induced through a structured protocol of extended access to self-administration of nicotine vapor (0.5 mg/ml) for 6 hours daily, establishing a reliable model for assessing withdrawal dynamics. Following the induction of dependence, animals underwent bilateral implantation of insulated stainless-steel electrodes within the NAc shell, subsequently receiving high-frequency DBS (60 μs pulse width, 130 Hz frequency, 150 μA current). A battery of behavioral assessments was conducted to evaluate hyperalgesia and the somatic signs of nicotine-induced withdrawal. Moreover, anxiety levels were assessed utilizing the elevated plus maze (EPM), alongside the quantification of irritability scores evaluated in both DBS and Sham-treated animals.The findings revealed a significant reduction in anxiety levels and a marked alleviation of both hyperalgesia and somatic withdrawal symptoms in the DBS group relative to the Sham-treated cohort. Given the established role of the NAc in reward processing, motivation, and the regulation of food intake, we hypothesized that stimulation in this region could impact body weight. Our data did not support this hypothesis, as body weight remained unaltered during the entire DBS manipulation in the NAc shell. Finally, DBS-treated animals showed less seeking behavior compared to the Sham-treated counterparts when reintroduced to the same cues associated with nicotine vapor delivery during nicotine vapor self-administration. These results substantiate the hypothesis that DBS of the NAc shell serves as an effective intervention for mitigating both psychological and physical withdrawal symptoms and may alleviate relapse, underscoring its potential as a multifaceted therapeutic strategy for addressing nicotine dependence. This study not only contributes to the understanding of neurobiological mechanisms underlying nicotine withdrawal but also opens avenues for innovative treatment modalities in addiction psychiatry.