ORIGINAL RESEARCH published: 20 April 2016 doi: 10.3389/fnagi.2016.00083 A Rat Model of Alzheimer’s Disease Based on Abeta 42 and Pro-oxidative Substances Exhibits Cognitive Deficit and Alterations in Glutamatergic and Cholinergic Neurotransmitter Systems Tomas Petrasek 1,2 *, Martina Skurlova 1 , Kristyna Maleninska 1 , Iveta Vojtechova 1 , Zdena Kristofikova 2 , Hana Matuskova 2 , Jana Sirova 2 , Karel Vales 1 , Daniela Ripova 2 and Ales Stuchlik 1 * 1 Department of Neurophysiology of Memory, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic, 2 National Institute of Mental Health, Klecany, Czech Republic Edited by: Paula I. Moreira, University of Coimbra, Portugal Reviewed by: Sónia C. Correia, University of Coimbra, Portugal Lucia Carboni, Alma Mater Studiorum University of Bologna, Italy *Correspondence: Tomas Petrasek disworlds@gmail.com; Ales Stuchlik ales.stuchlik@fgu.cas.cz Received: 20 January 2016 Accepted: 04 April 2016 Published: 20 April 2016 Citation: Petrasek T, Skurlova M, Maleninska K, Vojtechova I, Kristofikova Z, Matuskova H, Sirova J, Vales K, Ripova D and Stuchlik A (2016) A Rat Model of Alzheimer’s Disease Based on Abeta 42 and Pro-oxidative Substances Exhibits Cognitive Deficit and Alterations in Glutamatergic and Cholinergic Neurotransmitter Systems. Front. Aging Neurosci. 8:83. doi: 10.3389/fnagi.2016.00083 Alzheimer’s disease (AD) is one of the most serious human, medical, and socioeconomic burdens. Here we tested the hypothesis that a rat model of AD (Samaritan; Taconic Pharmaceuticals, USA) based on the application of amyloid beta 42 (Abeta 42 ) and the pro-oxidative substances ferrous sulfate heptahydrate and L-buthionine-(S, R)-sulfoximine, will exhibit cognitive deficits and disruption of the glutamatergic and cholinergic systems in the brain. Behavioral methods included the Morris water maze (MWM; long-term memory version) and the active allothetic place avoidance (AAPA) task (acquisition and reversal), testing spatial memory and different aspects of hippocampal function. Neurochemical methods included testing of the NR1/NR2A/NR2B subunits of NMDA receptors in the frontal cortex and CHT1 transporters in the hippocampus, in both cases in the right and left hemisphere separately. Our results show that Samaritan rats™ exhibit marked impairment in both the MWM and active place avoidance tasks, suggesting a deficit of spatial learning and memory. Moreover, Samaritan rats exhibited significant changes in NR2A expression and CHT1 activity compared to controls rats, mimicking the situation in patients with early stage AD. Taken together, our results corroborate the hypothesis that Samaritan rats are a promising model of AD in its early stages. Keywords: animal model, Alzheimer’s disease, sporadic AD, learning and memory, cognition, neurochemistry of the acetylcholine system, hippocampus Abbreviations: AAPA, active allothetic place avoidance; Abeta, amyloid beta; AD, Alzheimer’s disease; CHT1, high-affinity choline transporter; HACU, high-affinity choline uptake; MWM, Morris water maze; NMDA, N-methyl-D-aspartate. Frontiers in Aging Neuroscience | www.frontiersin.org 1 April 2016 | Volume 8 | Article 83