Differential effect of isoflurane, medetomidine, and urethane on BOLD responses to acute levo‐tetrahydropalmatine in the rat

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.