Levo-tetrahydropalmatine (l-THP) has shown significant promise in preclinical and clinical studies to treat drug addiction. Pharmacological MRI methods can elucidate the regional cerebral effects of l-THP, but there are potential confounds from the use of general anesthesia. To investigate the possible anesthetic–drug interactions for the pharmacological MRI result of acute l-THP, we examined acute blood oxygen level-dependent responses of both 5 and 20 mg/kg l-THP in naïve rats during general anesthesia achieved with three agents: isoflurane, medetomidine, and urethane. We found that with acute l-THP administration, isoflurane revealed the smallest blood oxygen level-dependent activation areas. In addition, urethane had the most activation areas; however, they were all negative. Medetomidine showed mixed positive and negative activations. Region-specific interactions were found between the l-THP-induced blood oxygen level-dependent responses and the anesthetic agents. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.