@article{MTMT:3148677, title = {Identifying non-toxic doses of manganese for manganese-enhanced magnetic resonance imaging to map brain areas activated by operant behavior in trained rats.}, url = {https://m2.mtmt.hu/api/publication/3148677}, author = {Gálosi, Rita and Szalay, László Csaba and Aradi, Mihály and Perlaki, Gábor and Pál, József and Steier, Roy and Lénárd, László and Karádi, Zoltán György}, doi = {10.1016/j.mri.2016.11.017}, journal-iso = {MAGN RESON IMAGING}, journal = {MAGNETIC RESONANCE IMAGING}, volume = {37}, unique-id = {3148677}, issn = {0730-725X}, 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 MnCl2 was 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 MnCl2 administrations. Manganese-enhanced images of each animal were subtracted from their baseline images to calculate decrease in the T1 value (DeltaT1) 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 MnCl2 showed hepatotoxic effect, but even these animals did not exhibit neurological symptoms. The dose of 20 and 40mg/kg MnCl2 increased 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 DeltaT1 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.}, year = {2017}, eissn = {1873-5894}, pages = {122-133} } @article{MTMT:2110764, title = {Tonic modulation of spinal hyperexcitability by the endocannabinoid receptor system in a rat model of osteoarthritis pain}, url = {https://m2.mtmt.hu/api/publication/2110764}, author = {Sagar, DR and Staniaszek, LE and Okine, BN and Woodhams, Stephen G and Norris, LM and Pearson, RG and Garle, MJ and Alexander, SP and Bennett, AJ and Barrett, DA and Kendall, DA and Scammell, BE and Chapman, V}, doi = {10.1002/art.27698}, journal-iso = {ARTH RHEUM/AR C RES}, journal = {ARTHRITIS AND RHEUMATISM}, volume = {62}, unique-id = {2110764}, issn = {0004-3591}, abstract = {OBJECTIVE: To investigate the impact of an experimental model of osteoarthritis (OA) on spinal nociceptive processing and the role of the inhibitory endocannabinoid system in regulating sensory processing at the spinal level. METHODS: Experimental OA was induced in rats by intraarticular injection of sodium mono-iodoacetate (MIA), and the development of pain behavior was assessed. Extracellular single-unit recordings of wide dynamic range (WDR) neurons in the dorsal horn were obtained in MIA-treated rats and saline-treated rats. The levels of endocannabinoids and the protein and messenger RNA levels of the main synthetic enzymes for the endocannabinoids (N-acyl phosphatidylethanolamine phospholipase D [NAPE-PLD] and diacylglycerol lipase alpha [DAGLalpha]) in the spinal cord were measured. RESULTS: Low-weight (10 gm) mechanically evoked responses of WDR neurons were significantly (P < 0.05) facilitated 28 days after MIA injection compared with the responses in saline-treated rats, and spinal cord levels of anandamide and 2-arachidonoyl glycerol (2-AG) were increased in MIA-treated rats. Protein levels of NAPE-PLD and DAGLalpha, which synthesize anandamide and 2-AG, respectively, were elevated in the spinal cords of MIA-treated rats. The functional role of endocannabinoids in the spinal cords of MIA-treated rats was increased via activation of cannabinoid 1 (CB(1) ) and CB(2) receptors, and blockade of the catabolism of anandamide had significantly greater inhibitory effects in MIA-treated rats compared with control rats. CONCLUSION: Our findings provide new evidence for altered spinal nociceptive processing indicative of central sensitization and for adaptive changes in the spinal cord endocannabinoid system in an experimental model of OA. The novel control of spinal cord neuronal responses by spinal cord CB(2) receptors suggests that this receptor system may be an important target for the modulation of pain in OA.}, keywords = {Animals; Male; RATS; Rats, Sprague-Dawley; Disease Models, Animal; Neurons/metabolism; Spinal Cord/*metabolism; Receptor, Cannabinoid, CB1/metabolism; Endocannabinoids/*metabolism; Glycerides/metabolism; Arachidonic Acids/metabolism; Receptor, Cannabinoid, CB2/metabolism; Polyunsaturated Alkamides/metabolism; Pain/etiology/*metabolism; Osteoarthritis/chemically induced/complications/*metabolism; Lipoprotein Lipase/metabolism; Iodoacetates/adverse effects}, year = {2010}, eissn = {1529-0131}, pages = {3666-3676} }