Effects of dizocilpine (MK801) on olfactory span in rats

MacQueen, David; Bullard, Laura A.; Galizio, Mark

doi:10.1016/j.nlm.2010.11.004

Cited by 40 publications

(79 citation statements)

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“…We found that administration of a competitive NMDA-r antagonist (CPP) produced dosedependent impairments in our variant of the OST. These findings are consistent with and extend prior odor span studies that have reported cognitive impairments in rats produced by competitive and noncompetitive NMDA-r antagonists (MacQueen et al 2011;Rushforth et al 2011;Davies et al 2013a;Galizio et al 2013) and enhanced performance in mice overexpressing the 2B NMDA-r subunit (Cui et al 2011). Notably, CPP did not affect reference memory performance, demonstrating the selective involvement of NMDA receptors in the working memory component of the task.…”

Section: Discussionsupporting

confidence: 91%

“…By limiting the number of comparisons presented on each trial, chance performance can be equated across trials of the task. Using this procedure, the negative association of performance and memory load has been confirmed (MacQueen et al 2011).Although the specific brain regions involved in this task have yet to be fully identified, there is evidence for the involvement of the prefrontal cortex and the hippocampus in the OST and its variations. Studies have shown that disruption of the medial prefrontal cortex (mPFC) by either chemical inactivation or administration of GluN2B antagonists impairs span without disrupting latency to choice or odor sensitivity in nonmatch-to-sample OST variations (Davies et al 2013a,b).…”

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confidence: 74%

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confidence: 80%

“…MacQueen et al (2011) examined the effects of the noncompetitive N-methyl-D-aspartate receptor (NMDA-r) antagonist MK-801 on an OST in rats. Their procedure included a control for sensorimotor and motivational drug effects in the form of well-learned two-comparison olfactory reference memory task [RMT; referred to by MacQueen et al (2011) as simple discrimination] inserted intermittently throughout a 24 trial (fixed-trial) OST procedure. Accurate responding in simple discrimination trials demonstrated intact motivation for reward, as well as sensorimotor competence and intact long-term memory.…”

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confidence: 99%

“…These studies demonstrate that working memory in the OST is selectively impaired by noncompetitive NMDA-r antagonists. However, one study characterizing the effects of MK-801 on performance across memory load failed to find an interaction between dose and memory load, suggesting that drug effects were not load-dependent (MacQueen et al 2011).…”

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confidence: 99%

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Influence of pharmacological manipulations of NMDA and cholinergic receptors on working versus reference memory in a dual component odor span task

et al. 2016

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Developed as a tool to assess working memory capacity in rodents, the odor span task (OST) has significant potential to advance drug discovery in animal models of psychiatric disorders. Prior investigations indicate OST performance is impaired by systemic administration of N-methyl-D-aspartate receptor (NMDA-r) antagonists and is sensitive to cholinergic manipulations. The present study sought to determine whether an impairment in OST performance can be produced by systemic administration of the competitive NMDA-r antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP; 3, 10, 17 mg/kg i.p.) in a unique dual-component variant of the OST, and whether this impairment is ameliorated by nicotine (0.75 mg/kg i.p.). Male Sprague-Dawley rats were trained to asymptotic level of performance on a 24-trial two-comparison incrementing nonmatching to sample OST. In addition, rats were administered a two-comparison olfactory reference memory (RM) task, which was integrated into the OST. The RM task provided an assessment of the effects of drug administration on global behavioral measures, long-term memory and motivation. Several measures of working memory (span, longest run, and accuracy) were dose dependently impaired by CPP without adversely affecting RM. Analysis of drug effects across trial blocks demonstrated a significant impairment of performance even at low memory loads, suggesting a CPP-induced deficit of olfactory short-term memory that is not load-dependent. Although nicotine did not ameliorate CPP-induced impairments in span or accuracy, it did block the impairment in longest run produced by the 10 mg/kg dose of CPP. Overall, our results indicate that performance in our 24 odor two-comparison OST is capacity dependent and that CPP impaired OST working, but not reference, memory.The odor span task, which was originally developed by Dudchenko et al. (2000), makes use of a primary sensory modality for rodents (olfaction) to assess the neurobiological and neuropharmacological basis of rodent memory. In the original procedure, rats were trained to dig in cups of sand, each mixed with a different household spice (e.g., basil or paprika), to retrieve buried food rewards. On each successive trial, a novel odor was presented, along with every odor that had been presented in preceding trials, but only responses to the novel odor were reinforced. To respond accurately on any given trial the rat needed to remember each stimulus it had encountered earlier in the session and withholds responses to these stimuli. Therefore, memory demands escalated over the course of the procedure as the number of odors the rat was required to remember increased. Dudchenko et al. (2000) demonstrated that performance in the task declined across trials, indicating that task accuracy was negatively impacted by increasing memory load. However, in this OST procedure, the number of comparisons presented on each successive trial increases in tandem with the number of stimuli to remember, confounding the relationship between accuracy and mem...

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Section: Discussionsupporting

confidence: 91%

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confidence: 74%

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confidence: 80%

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confidence: 99%

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confidence: 99%

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Influence of pharmacological manipulations of NMDA and cholinergic receptors on working versus reference memory in a dual component odor span task

et al. 2016

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The protocol for assessing olfactory working memory capacity in mice

et al. 2022

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Background Working memory capacity (WMC) is the ability to maintain information over a few seconds. Although it has been extensively studied in healthy subjects and neuropsychiatric patients, few tasks have been developed to measure such changes in rodents. Many procedures have been used to measure WM in rodents, including the radial arm maze, the WM version of the Morris swimming task, and various delayed matching and nonmatching‐to‐sample tasks. It should be noted, however, that the memory components assessed in these procedures do not include memory capacity. Methods We developed an olfactory working memory capacity (OWMC) paradigm to assess the WMC of 3‐month‐old 5×FAD mice, a mouse model of Alzheimer's disease. The task is divided into five phases: context adaptation, digging training, rule learning for nonmatching to a single sample odor (NMSS), rule learning for nonmatching to multiple sample odors (NMMS), and capacity testing. Results In the NMSS rule‐learning phase, there was no difference between wild‐type (WT) mice and 5×FAD mice in the performance correct rate, correct option rate, and correct rejection rate. The WT mice and 5×FAD mice showed similar memory capacity in the NMMS rule‐learning phase. After capacity test, we found that the WMC was significantly diminished in 5×FAD mice. As the memory load increased, 5×FAD mice also made significantly more errors than WT mice. Conclusion The OWMC task, based on a nonmatch‐to‐sample rule, is a sensitive and robust behavioral assay that we validated as a reliable method for measuring WMC and exploring different components of memory in mice.

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The Olfactory Working Memory Capacity Paradigm

Jiang,

Huang,

2024

Current Protocols

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Working memory capacity (WMC), a crucial component of working memory (WM), has consistently drawn the attention of researchers. Exploring the underlying neurobiological mechanisms behind it is currently a prominent focus in the field of neuroscience. Previously, we developed a novel behavioral paradigm for rodents called the olfactory working memory capacity (OWMC) paradigm, which serves as an effective tool for quantifying the WMC of rodents. The OWMC task comprises five phases: context adaptation, digging training, rule‐learning for nonmatching to a single sample odor (NMSS), rule‐learning for nonmatching to multiple sample odors (NMMS), and capacity testing. In the first phase, mice are handled to reduce stress and acclimate to the training cage. The second phase involves training mice to dig in a bowl of unscented sawdust to locate a piece of cheese. In the third phase, mice are trained to locate the cheese pellet in a bowl with a noveal odor. The fourth phase requires mice to distinguish the novel odor among multiple scented bowls to locate the cheese pellet. Finally, in the fifth phase, mice undergo several WMC tests until they achieve a stable level of performance. In this protocol paper, we will provide detailed instructions on how to implement the behavioral paradigm. © 2024 Wiley Periodicals LLC.Basic Protocol 1: Context adaptationBasic Protocol 2: Digging trainingBasic Protocol 3: Rule‐learning for NMSSBasic Protocol 4: Rule‐learning for NMMSBasic Protocol 5: Capacity testing

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Effects of dizocilpine (MK801) on olfactory span in rats

Cited by 40 publications

References 32 publications

Influence of pharmacological manipulations of NMDA and cholinergic receptors on working versus reference memory in a dual component odor span task

Influence of pharmacological manipulations of NMDA and cholinergic receptors on working versus reference memory in a dual component odor span task

The protocol for assessing olfactory working memory capacity in mice

The Olfactory Working Memory Capacity Paradigm

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