On the use of α-chloralose for repeated BOLD fMRI measurements in rats

Most animal experiments in neurosciences require anesthesia of the experimental animal. For fMRI experiments most neuroscientist would prefer (I) a recoverable anesthesia that would (II) allow strong BOLD responses which are (III) reproducibly obtained for the same animal in repetitive experiments. Strong BOLD responses are particularly needed if weak physiological stimuli like whisker deflection are used. A-chloralose, in contrast to isoflurane, fulfils the need for strong activation but has been traditionally considered as a terminal drug due to its negative physiological side effects. Here it is demonstrated, that new commercial α-chloralose in a careful application scheme allows for repeated fMRI studies on the same animal with similar responses after whisker stimulation. Only minor effects on the normal behavior were observed between drugs. These include a longer time to return to baseline values of food ingestion and slower tail reaction for the α-chloralose experiments.

[1]  A. Hudetz,et al.  Laser-Doppler Measurement of the Effects of Halothane and Isoflurane on the Cerebrovascular CO2 Response in the Rat , 1995, Anesthesia and analgesia.

[2]  H. L. Williams,et al.  Alpha chloralose and nocturnal physiological patterns , 2004, Psychopharmacologia.

[3]  Bert Sakmann,et al.  Whisker maps of neuronal subclasses of the rat ventral posterior medial thalamus, identified by whole‐cell voltage recording and morphological reconstruction , 2002, The Journal of physiology.

[4]  Tao Jin,et al.  Isoflurane anesthesia effect in functional imaging studies , 2007, NeuroImage.

[5]  I. Aroch,et al.  Alpha-chloralose poisoning in dogs and cats: a retrospective study of 33 canine and 13 feline confirmed cases. , 2006, Veterinary journal.

[6]  Russell R. Monroe,et al.  The pharmacology of chloralose , 1964, Psychopharmacologia.

[7]  Bharat B. Biswal,et al.  A protocol for use of medetomidine anesthesia in rats for extended studies using task-induced BOLD contrast and resting-state functional connectivity , 2009, NeuroImage.

[8]  J. Keating,et al.  Alpha-chloralose is a suitable anesthetic for chronic focal cerebral ischemia studies in the rat: A comparative study , 2008, Brain Research.

[9]  Seong-Gi Kim,et al.  Dose‐dependent effect of isoflurane on neurovascular coupling in rat cerebral cortex , 2009, The European journal of neuroscience.

[10]  A Kriss,et al.  Comparison of the effects of four anaesthetic agents on somatosensory evoked potentials in the rat , 1999, Laboratory animals.

[11]  A Schnitzler,et al.  Brain activation patterns underlying fast habituation to painful laser stimuli. , 2010, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[12]  Dennis F. Kohn,et al.  Anesthesia and analgesia in laboratory animals , 2008 .

[13]  Andreas Hess,et al.  A Genome-wide Drosophila Screen for Heat Nociception Identifies α2δ3 as an Evolutionarily Conserved Pain Gene , 2010, Cell.

[14]  Mathias Hoehn,et al.  High field BOLD response to forepaw stimulation in the mouse , 2010, NeuroImage.

[15]  C. Leithner,et al.  A flow sensitive alternating inversion recovery (FAIR)-MRI protocol to measure hemispheric cerebral blood flow in a mouse stroke model , 2008, Experimental Neurology.

[16]  Peter Herman,et al.  Energetics of neuronal signaling and fMRI activity , 2007, Proceedings of the National Academy of Sciences.

[17]  C. Ferris,et al.  Comparison of evoked cortical activity in conscious and propofol‐anesthetized rats using functional MRI , 1999, Magnetic resonance in medicine.

[18]  Dirk Wiedermann,et al.  A fully noninvasive and robust experimental protocol for longitudinal fMRI studies in the rat , 2006, NeuroImage.

[19]  N. Harrison,et al.  The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations , 2000, British journal of pharmacology.

[20]  I. Fried,et al.  Coupling between Neuronal Firing Rate, Gamma LFP, and BOLD fMRI Is Related to Interneuronal Correlations , 2007, Current Biology.

[21]  C. Tommasino,et al.  Local Cerebral Blood Flow and Glucose Utilization during Isoflurane Anesthesia in the Rat , 1986, Anesthesiology.

[22]  N. Logothetis,et al.  Neurophysiological investigation of the basis of the fMRI signal , 2001, Nature.

[23]  M. Ueki,et al.  Effect of alpha‐chloralose, halothane, pentobarbital and nitrous oxide anesthesia on metabolic coupling in somatosensory cortex of rat , 1992, Acta anaesthesiologica Scandinavica.

[24]  A. Hudetz,et al.  In Vivo Effects of Dexmedetomidine on Laser‐Doppler Flow and Pial Arteriolar Diameter , 1998, Anesthesiology.