title: Identifying non-toxic doses of manganese for manganese-enhanced magnetic resonance imaging to map brain areas activated by operant behavior in trained rats.
abstract: Manganese-enhanced magnetic resonance imaging (MEMRI) offers unique advantages such as studying brain activation in freely moving rats, but its usefulness has not been previously evaluated during operant behavior training. Manganese in a form of MnCl2, at a dose of 20mg/kg, was intraperitoneally infused. The administration was repeated and separated by 24h to reach the dose of 40mg/kg or 60mg/kg, respectively. Hepatotoxicity of the MnCl2was evaluated by determining serum aspartate aminotransferase, alanine aminotransferase, total bilirubin, albumin and protein levels. Neurological examination was also carried out. The animals were tested in visual cue discriminated operant task. Imaging was performed using a 3T clinical MR scanner. T1 values were determined before and after MnCl2administrations. Manganese-enhanced images of each animal were subtracted from their baseline images to calculate decrease in the T1 value (ΔT1) voxel by voxel. The subtracted T1 maps of trained animals performing visual cue discriminated operant task, and those of naive rats were compared. The dose of 60mg/kg MnCl2showed hepatotoxic effect, but even these animals did not exhibit neurological symptoms. The dose of 20 and 40mg/kg MnCl2increased the number of omissions and did not affect the accuracy of performing the visual cue discriminated operant task. Using the accumulated dose of 40mg/kg, voxels with a significant enhanced ΔT1 value were detected in the following brain areas of the visual cue discriminated operant behavior performed animals compared to those in the controls: the visual, somatosensory, motor and premotor cortices, the insula, cingulate, ectorhinal, entorhinal, perirhinal and piriform cortices, hippocampus, amygdala with amygdalohippocampal areas, dorsal striatum, nucleus accumbens core, substantia nigra, and retrorubral field. In conclusion, the MEMRI proved to be a reliable method to accomplish brain activity mapping in correlation with the operant behavior of freely moving rodents.
authors.affiliation: Institute of Physiology, Medical School of University of Pécs, Pécs, Hungary. Electronic address: rita.galosi@aok.pte.hu.
authors.forename: Rita
authors.initials: R
authors.lastname: Gálosi
authors.affiliation: Institute of Physiology, Medical School of University of Pécs, Pécs, Hungary. Electronic address: tsabbie@gmail.com.
authors.forename: Csaba
authors.initials: C
authors.lastname: Szalay
authors.affiliation: Pécs Diagnostic Center, Pécs, Hungary. Electronic address: misi.aradi@gmail.com.
authors.forename: Mihály
authors.initials: M
authors.lastname: Aradi
authors.affiliation: Neurosurgery Clinic, Medical School of University of Pécs, Pécs, Hungary; Pécs Diagnostic Center, Pécs, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Perlaki
authors.affiliation: Neurosurgery Clinic, Medical School of University of Pécs, Pécs, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Pál
authors.affiliation: Neurosurgery Clinic, Medical School of University of Pécs, Pécs, Hungary. Electronic address: roy.steier@gmail.com.
authors.forename: Roy
authors.initials: R
authors.lastname: Steier
authors.affiliation: Institute of Physiology, Medical School of University of Pécs, Pécs, Hungary; Molecular Neuroendocrinology and Neurophysiology Research Group, Szentágothai Research Center, University of Pécs, Pécs, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Lénárd
authors.affiliation: Institute of Physiology, Medical School of University of Pécs, Pécs, Hungary; Molecular Neuroendocrinology and Neurophysiology Research Group, Szentágothai Research Center, University of Pécs, Pécs, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Karádi
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods*; D003216:Conditioning, Operant / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008345:Manganese / Q000008:administration & dosage* / Q000633:toxicity; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008345:Manganese
keywords: Magnetic resonance imaging; Manganese; Operant behavior; Rats; Toxicity