A systematic review of physiological methods in rodent pharmacological MRI studies

Abstract

RationalePharmacological magnetic resonance imaging (phMRI) provides an approach to study effects of drug challenges on brain processes. Elucidating mechanisms of drug action helps us to better understand the workings of neurotransmitter systems, map brain function or facilitate drug development. phMRI is increasingly used in preclinical research employing rodent models; however, data interpretation and integration are complicated by the use of different experimental approaches between laboratories. In particular, the effects of different anaesthetic regimes upon neuronal and haemodynamic processes and baseline physiology could be problematic.ObjectivesThis paper investigates how differences in phMRI research methodologies are manifested and considers associated implications, placing particular emphasis on choice of anaesthetic regimes.MethodsA systematic review of rodent phMRI studies was conducted. Factors such as those describing anaesthetic regimes (e.g. agent, dosage) and parameters relating to physiological maintenance (e.g. ventilatory gases) and MRI method were recorded.ResultsWe identified 126 eligible studies and found that the volatile agents isoflurane (43.7 %) and halothane (33.3 %) were most commonly used for anaesthesia, but dosage and mixture of ventilatory gases varied substantially between laboratories. Relevant physiological parameters were usually recorded, although 32 % of studies did not provide cardiovascular measures.ConclusionsAnaesthesia and animal preparation can influence phMRI data profoundly. The variation of anaesthetic type, dosage regime and ventilatory gases makes consolidation of research findings (e.g. within a specific neurotransmitter system) difficult. Standardisation of a small(er) number of preclinical phMRI research methodologies and/or increased consideration of approaches that do not require anaesthesia is necessary to address these challenges.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-014-3855-0) contains supplementary material, which is available to authorized users.

Functional network study on the wild type and DISC1 transgenic mice

“…Various anaesthetics have their own advantages and disadvantages, and differentially influence the animal's normal homeostasis and brain activity (Mueggler et al, 2012;Haensel et al, 2015).…”

“…Halothane and isoflurane are inhalation anaesthetics commonly used in studies involving animals, among which isoflurane is the mostly used anaesthetic in laboratory animals (Tremoleda et al, 2012;Haensel et al, 2015). Therefore, isoflurane, medetomidine, propofol and urethane will be further reviewed in this section.…”

“…However, it is a well-known vasodilatory agent that increases the baseline cerebral blood flow in a dose-dependent way, and hence may influence neurovascular interactions that could be detected by fMRI technique. Isoflurane also suppresses neural activity which confounds rs-fMRI results (Haensel et al, 2015;Pan et al, 2015). Like other general anaesthetics, the precise molecular mechanism of action of isoflurane is not clearly understood.…”

“…Like other general anaesthetics, the precise molecular mechanism of action of isoflurane is not clearly understood. Although it targets multiple receptor systems, the major component of its mode of action is modulation of  -aminobutyric acid type A (GABA(A)) receptors (Richards, 2002;Ballesteros et al, 2012;Haensel et al, 2015). Despite its disadvantages, isoflurane is still a very useful agent.…”

“…Alpha-chloralose is not suitable for longitudinal studies due to its depressive effects on respiration and toxicity (Haensel et al, 2015;Pan et al, 2015;Petrinovic et al, 2016). One recent study reported that this agent led to unstable physiological maintenance of mice for fMRI studies when compared to isoflurane (Low et al, 2016a).…”