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

Abstract

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.

Differential responses to acute administration of a new 5-HT7-R agonist as a function of adolescent pre-treatment: phMRI and immuno-histochemical study

“…Unfortunately, general anesthesia may perturb cerebral blood flow and metabolism, as well as electro-physiological, cardio respiratory, and other physiological parameters; finally, it can suppress neuronal activity reducing the BOLD response (Gozzi et al, 2008 ). Recent studies reveal that BOLD response to the same challenge may change from negative to positive, or differ in amplitude, with different anesthetic regimes (Sommers et al, 2009 ; Hodkinson et al, 2012 ; Liu et al, 2012 ). Also, the pharmacological challenge in itself can produce cardio respiratory physiological responses that may alter hemodynamic measurements in brain.…”

A systematic review of physiological methods in rodent pharmacological MRI studies

“…Caution is thus required when interpreting preclinical phMRI data, where observed signal changes may reflect an interaction of the effects of the anaesthetic agent and those of the drug under study. Indeed several studies have presented differential responses to pharmacological challenge under varying anaesthetic regimes (Gordon et al 1995 ; Gozzi et al 2008 ; Du et al 2009 ; Liu et al 2012 ; Hodkinson et al 2012 ). Intravenous cocaine, for instance, evoked CBF increases in alpha-chloralose-anaesthetised rats, but reduced CBF under isoflurane (Du et al 2009 ).…”

Enhanced Thalamic Functional Connectivity with No fMRI Responses to Affected Forelimb Stimulation in Stroke-Recovered Rats

“…Similarly, such a complete absence of plastic and/or reorganized hemodynamic fMRI activity in the ipsi-lesional hemisphere was also previously observed and longitudinally validated by Weber et al (2008) using both BOLD fMRI and electrophysiology. Although choice of anesthesia was discussed as a possible source of the suppression of plastic response by Weber et al (2008) who used medetomidine (vs. alpha-chloralose by Dijkhuizen et al) (Tsurugizawa et al, 2010; Liu et al, 2012), the prolonged lack of neural signals that should account for the apparent neurological recovery was neither questioned nor discussed in their study. Even our present scrutiny on this issue using both BOLD and CBVw fMRI techniques in the behaviorally recovered rats under the same anesthesia regimen previously used by Dijkhuizen et al did not reveal any relevant fMRI signals.…”