Abnormal brain functional activity and changes in c-Fos expression of propofol dependence in rats

Propofol demonstrates dependence at subclinical anesthetic doses, however, the underlying neural mechanisms remain unclear. In this study, we established a self-administration model of propofol in Sprague-Dawley (SD) rats, used a combination of the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) analysis approach of resting-state functional magnetic resonance imaging (rs-fMRI) to examine the local brain functional activity changes, Western Blot (WB) was used to detect the change of c-Fos protein expression in the prefrontal cortex and hippocampus. Results showed that the propofol-dependent rats exhibited enhanced seeking behaviour and decreased spontaneous locomotor activity compared to saline control group, while increased ALFF values in the bilateral prefrontal cortex and right hippocampus, and increased ReHo values in the left striatum and pons. c-Fos gene expression in the prefrontal cortex was significantly increased in propofol-dependent rats compared with controls. In conclusion, enhanced seeking behaviour and decreased spontaneous locomotor activity in propofol-dependent rats may lead to abnormal functional activity and upregulation of c-Fos expression in the prefrontal cortex. These findings may shed light on propofol-dependent brain dysfunction from the perspective of local brain activity, emphasizing the potential usefulness of combining functional MRI and c-Fos expression in elucidating the neuropathological mechanisms of propofol dependence and may ultimately inform future disease treatment of propofol addiction. • Rs-fMRI ALFF/ReHo and c-Fos expression study in propofol dependence • Propofol rats show enhanced drug-seeking and reduced locomotor activity • Increased ALFF in prefrontal cortex and hippocampus of dependent rats • Upregulated c-Fos expression specifically in prefrontal cortex • Combined neuroimaging-molecular approach reveals addiction brain mechanisms