title: Measure of anxiety-related behaviors and hippocampal BDNF levels associated to the amnesic effect induced by MK-801 evaluated in the modified elevated plus-maze in rats.
abstract: Non-competitive N-methyl-d-aspartate receptor (NMDA-R) antagonists impair rodent cognition. Specifically, MK-801, the most potent NMDA-R antagonist, induces an amnesic effect on the modified elevated plus maze (mEPM) learning test in rodents, which reflects spatial long-term memory. However, alterations in anxiety-related behaviors could overlap this amnesic effect. Accumulated evidence supports the role of brain-derived neurotrophic factor (BDNF) in learning and memory processes and deficits in hippocampal BDNF function, which underlie cognitive impairments, have been extensively reported. Therefore, we investigated if changes in anxiety-related behaviors and hippocampal BDNF levels are related with the amnesic effect induced by MK-801 in the mEPM.Transfer latency (TL) as an index of spatial memory in the mEPM was used. TL1 was evaluated 30 min after saline/MK-801 injection (day 1, acquisition session) while learning/memory performance was measured 24 h later at TL2 (day 2, retention session). Also at TL2, two other experimental groups were added to measure the anxiety-related behaviors using the classic EPM and BDNF protein levels by ELISA. To evaluate if amnesia endures, an additional session was recorded on day 3 (TL3) and BDNF levels were measured.While TL1 was not significantly modified by MK-801, TL2 was increased compared to the control group indicating an amnesic effect. This effect was not mimicked by anxiety-related behaviors and it was associated to a significant attenuation of BDNF levels. During the third post-training day, the cognitive performance of MK-801-treated animals was improved and an increased BDNF protein expression in the hippocampus accompanied this change
authors.affiliation: Department of Experimental Neuropharmacology, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, 11600 Montevideo, Uruguay. Electronic address: xlopez@iibce.edu.uy.
authors.forename: Ximena López
authors.initials: XL
authors.lastname: Hill
authors.affiliation: Laboratory of Cell Biology, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, 11600 Montevideo, Uruguay. Electronic address: aricheri@iibce.edu.uy.
authors.forename: Analía
authors.initials: A
authors.lastname: Richeri
authors.affiliation: Department of Experimental Neuropharmacology, Instituto de Investigaciones Biológicas Clemente Estable, Avenida Italia 3318, 11600 Montevideo, Uruguay. Electronic address: cscorza@iibce.edu.uy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Scorza
mesh_terms: D000647:Amnesia / Q000139:chemically induced*; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000175:diagnosis*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000633:toxicity*; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D005106:Exploratory Behavior / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate
keywords: Amnesia; Cognition; ELISA; NMDA receptor antagonist; Plus-maze