Peripheral lipopolysaccharide administration impairs two-way active avoidance conditioning in C57BL/6J mice.
ABSTRACT Peripheral administration of lipopolysaccharide (LPS) or interleukin-1 (IL-1) may lead to alterations of CNS function and behavioral changes designated "sickness behavior." Further, some experiments show evidence of LPS- and cytokine-mediated alterations in learning and memory. The current series of experiments examined the effects of a single or repeated intraperitoneal LPS injections, at a number of doses and time points before or after test sessions, on behavior in a two-way active avoidance conditioning paradigm. Subjects were able to avoid the mild shock stimulus, escape it, or fail to respond to it. Subjects treated with LPS at many, but not all, of the time points sampled showed impaired learning, by exhibiting significantly fewer avoidance responses than controls. Furthermore, an LPS-induced increase in non-cued inter-trial interval crossings was observed during the later days of testing, suggesting that a greater percentage of their avoidance responses was not conditioned and their behavior was less efficient. Taken together, the results suggest that LPS-treated animals showed a diminished association between conditioned stimulus (CS) and unconditioned stimulus (US). These results support the theory that peripheral immune stimuli may induce deleterious effects on learning, and extend the work to a negatively reinforced operant procedure.
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ABSTRACT: Recent evidence suggests that inflammation-induced decrements in cognitive function can be mitigated via manipulation of excitatory or inhibitory transmission. We tested the ability of the inverse benzodiazepine agonist, MRK-016 (MRK) to protect against LPS-induced deficits in memory acquisition and consolidation, using a contextual fear conditioning (CFC) paradigm. In Experiment One, mice received lipopolysaccharide (LPS) and/or MRK injections prior to CFC training, and were then tested 24hours after training. In Experiment Two, animals received similar treatment injections immediately after training, and were tested 24hours later. Additionally, hippocampal samples were collected four hours after LPS injections and immediately after testing, to evaluate brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1) mRNA expression. Results indicate that MRK can protect against LPS-induced learning/memory decrements in both paradigms. We also found, in both paradigms, that animals treated with LPS/Saline expressed significantly less BDNF mRNA when compared to Saline/Saline-treated animals four hours after LPS administration, but that MRK did not restore BDNF expression levels. Further, treatment administrations had no effect on IGF-1 mRNA expression at any collection time-point. In summary, MRK-016 can protect against LPS-induced deficits in memory acquisition and consolidation, in this hippocampus-dependent paradigm, though this protection occurs independently of recovery of BDNF expression. Copyright © 2015. Published by Elsevier B.V.Behavioural brain research 03/2015; 288. DOI:10.1016/j.bbr.2015.03.048 · 3.39 Impact Factor
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ABSTRACT: Even though laboratory evolution experiments have demonstrated genetic variation for learning ability, we know little about the underlying genetic architecture and genetic relationships with other ecologically relevant traits. With a full diallel cross among twelve inbred lines of Drosophila melanogaster originating from a natural population (0.75 < F < 0.93), we investigated the genetic architecture of olfactory learning ability and compared it to that for another behavioral trait (unconditional preference for odors), as well as three traits quantifying the ability to deal with environmental challenges: egg-to-adult survival and developmental rate on a low-quality food, and resistance to a bacterial pathogen. Substantial additive genetic variation was detected for each trait, highlighting their potential to evolve. Genetic effects contributed more than nongenetic parental effects to variation in traits measured at the adult stage: learning, odorant perception, and resistance to infection. In contrast, the two traits quantifying larval tolerance to low-quality food were more strongly affected by parental effects. We found no evidence for genetic correlations between traits, suggesting that these traits could evolve at least to some degree independently of one another. Finally, inbreeding adversely affected all traits.Ecology and Evolution 02/2015; 5(3). DOI:10.1002/ece3.1379 · 1.66 Impact Factor
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ABSTRACT: In the current study, the partial NMDA receptor agonist D-cycloserine (DCS) rescued memory consolidation following systemic bacterial endotoxin exposure. DCS failed, however, to restore hippocampal BDNF mRNA levels that were diminished following a systemic administration of LPS, and did not alter NR1 or NR2C NMDA receptor subunit expression. These results extend prior research into the role of DCS in neural-immune interactions, and indicate that the detrimental effects of peripheral LPS administration on consolidation of contextual fear memory may be ameliorated with DCS treatment, though the mechanisms underlying these effects are currently unclear.Behavioural brain research 01/2013; 243. DOI:10.1016/j.bbr.2012.12.053 · 3.39 Impact Factor