Site-Selective N-Methyl-?-Aspartate and α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionate Antagonists Produce Distinct Effects in Rats Performing Complex Discriminations

Willmore, Catherine B.; Bespalov, Anton; Beardsley, Patrick M.

doi:10.1006/nlme.2002.4077

Cited by 8 publications

(6 citation statements)

References 92 publications

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“…Our finding that NBQX alone has no effect on contextual fear conditioning and latent inhibition supports previous studies that report no learning-related memory impairments associated with AMPAR antagonism by NBQX (Parada et al 1992;Misztal and Danysz 1995;Stephens and Cole 1996;Lu and Wehner 1997;Filliat et al 1998;Mead and Stephens 1999;Pitsikas et al 2002;Willmore et al 2002;Gutierrez et al 2004), even though NBQX has a high affinity for AMPARs and inhibits glutamate and AMPA-associated currents (Sheardown et al 1990;Parsons et al 1994;Rammes et al 1998). However, it should be noted that some behavioral tasks have been shown to be sensitive to the AMPA/kainate receptor antagonist CNQX.…”

Section: Ampars: Acquisition and Consolidationsupporting

confidence: 90%

“…However, in humans, the maximally tolerated dose of the AMPA/kainate antagonist LY293538 did not disrupt cognitive function (Sang et al 1998). In addition, behavioral studies and LTP studies that have used antagonists with greater selectivity for AMPARs than kainate receptors have not consistently found learning-related memory impairments or deficits in LTP (Parada et al 1992; for review of AMPARs and learning, see Danysz et al 1995;Misztal and Danysz 1995;Sato et al 1995;Stephens and Cole 1996;Li et al 1997;Lu and Wehner 1997;Filliat et al 1998;Mead and Stephens 1999;Kapus et al 2000;Lees 2000;Aultman and Moghaddam 2001;Pitsikas et al 2002;Willmore et al 2002;Gutierrez et al 2004). For example, Lu and Wehner (1997) found that in C57BL/6 mice, cued and contextual fear conditioning was insensitive to the AMPAR antagonist NBQX at a dose three times higher than a dose of NBQX that produced 100% protection against audiogenic seizures in mice (Swedberg et al 1995).…”

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confidence: 99%

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Coantagonism of glutamate receptors and nicotinic acetylcholinergic receptors disrupts fear conditioning and latent inhibition of fear conditioning

Gould¹,

Lewis

2005

Learn. Mem.

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The present study investigated the hypothesis that both nicotinic acetylcholinergic receptors (nAChRs) and glutamate receptors (␣-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) and N-methyl-Daspartate glutamate receptors (NMDARs)) are involved in fear conditioning, and may modulate similar processes. The effects of the nAChR antagonist mecamylamine administered alone, the AMPAR antagonist NBQX administered alone, and the NMDAR antagonist MK-801 administered alone on cued fear conditioning, contextual fear conditioning, and latent inhibition of cued fear conditioning were examined. In addition, the effects of coadministration of either mecamylamine and NBQX or mecamylamine and MK-801 on these behaviors were examined. Consistent with previous studies, neither mecamylamine nor NBQX administered alone disrupted any of the tasks. However, coadministration of mecamylamine and NBQX disrupted both contextual fear conditioning and latent inhibition of cued fear conditioning. In addition, coadministration of mecamylamine with a dose of MK-801 subthreshold for disrupting either task disrupted both contextual fear conditioning and latent inhibition of cued fear conditioning. Coadministration of mecamylamine and NBQX, and coadministration of mecamylamine with a dose of MK-801 subthreshold for disrupting fear conditioning had little effect on cued fear conditioning. These results suggest that nAChRs and glutamate receptors may support similar processes mediating acquisition of contextual fear conditioning and latent inhibition of fear conditioning.A large body of research has been directed at understanding the neural, cellular, and molecular processes that underlie fear conditioning and tasks that modulate conditioning, such as latent inhibition. This focus provides a means to not only understand the neurobiology of learning, but also to understand disease states that can be modeled with these tasks. Fear conditioning measures amygdala-and hippocampus-dependent learning (contextual fear conditioning), as well as amygdala-dependent and hippocampus-independent learning (cued fear conditioning) within the same subject (Kim and

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Section: Ampars: Acquisition and Consolidationsupporting

confidence: 90%

mentioning

confidence: 99%

Coantagonism of glutamate receptors and nicotinic acetylcholinergic receptors disrupts fear conditioning and latent inhibition of fear conditioning

Gould¹,

Lewis

2005

Learn. Mem.

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“…DCS was previously found to enhance NMDAR activation and to facilitate the expression of synaptic plasticity in the hippocampus of young adult animals (Rouaud & Billard, 2003), as confirmed in the present study. In addition to increasing the excitability of hippocampal neurons (Pitkänen et al ., 1994), this facilitation of plasticity processing within neuronal networks therefore represents a potential cellular mechanism allowing DCS to improve memory performances in adult animals (Thompson et al ., 1992; Riekkinen et al ., 1998; Lelong et al ., 2001; Willmore et al ., 2002; Lee et al ., 2006). DCS not only facilitated NMDAR activation and synaptic plasticity in young rats, but was significantly more potent in aged animals; thus reversing the age‐related deficit of NMDAR‐mediated synaptic potentials as well as those of LTP and LTD.…”

Section: Discussionmentioning

confidence: 99%

Deficit of NMDA receptor activation in CA1 hippocampal area of aged rats is rescued by d‐cycloserine

Rouaud

2007

Eur J of Neuroscience

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Activation of the glycine modulatory site of the N-methyl-D-aspartate glutamate receptor (NMDAR) may reduce cognitive impairments associated with normal ageing. In order to test this hypothesis, we assessed the effects of the partial agonist D-cycloserine (DCS) on cellular activities involved in memory formation. This was performed in CA1 cellular networks of adult and aged Sprague-Dawley rat hippocampal slices using extracellular field excitatory postsynaptic potential recordings. Synaptic potentials specifically mediated by NMDAR were significantly reduced in aged animals. DCS increased the magnitude of these responses in both adult and old rats but this effect was significantly higher in the latter, thus reversing the age-related decrease in NMDAR synaptic potentials. NMDAR-mediated theta burst long-term potentiation (TBS-LTP) as well as long-term depression (LTD) of synaptic transmission, prominent models for the cellular basis of learning and memory, were also weakened in aged animals. Age-related alterations of both forms of synaptic plasticity were rescued by DCS. In addition, the DCS-induced decrease in basal fast glutamatergic neurotransmission involving the activation of inhibitory glycinergic receptors, previously reported in young rats (Rouaud & Billard, 2003), was severely attenuated in aged animals. In summary, our results indicate that the facilitation of NMDAR activation through its glycine-binding site rescues the age-related deficit of cellular mechanisms of learning and memory. Such physiological evidences suggest that this modulation site of NMDAR represents an important target to alleviate cognitive deficits associated with normal ageing.

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“…The accuracy of choice behavior was also analyzed using signal detection analysis (SD) methods similar to those used in other complex discriminations (Willmore et al 2002; Kirk et al 1988; Watson and Blampied 1989; Tan et al 1989; White et al 1989; Poorheidari et al 1998). For our SD measurements, response bias (log bias) and a bias-free measure of discriminability (log d , referred to as d ′ in the present paper) were calculated using the following equation:

d^{'} = 0.5 log ([C_{high} \times C_{low}] \div [E_{high} \times E_{low}])

…”

Section: Methodsmentioning

confidence: 99%

Cognitive effects of psychotomimetic drugs in rats discriminating number cues

et al. 2008

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Rationale Deficits in memory and attention are broadly acknowledged during psychosis; however, experiments on modeled psychosis often test working memory without systematic manipulation of attentional demands. Objectives The major research goal was discovering which neurobehavioral processes, attention, or memory contributed more to drug-provoked performance deficits. Materials and methods Rats were trained to perform operant ratio discrimination (RD) tasks wherein the number of presses at a rear-wall lever was discriminated using one of two front-wall levers. Effects from four psychotomimetic drugs, the serotonin agonist 2,5-dimethoxy-4-iodoamphetamine, the noncompetitive NMDA-glutamate receptor antagonist phencyclidine (PCP), and two CB1-selective cannabinoid agonists, WIN 55,512-2 and AM 411, were assessed using a signal detection analytical overlay to dissociate cognitive from noncognitive motor and motivational disruptions. Further methods allowed dissociation of attention compromises from mnemonic deficits. Results For each test compound, at least one dose elicited decreased RD accuracy without affecting response rates, and task difficulty was shown to be a crucial dictator of accuracy effect specificities. Effects from both PCP and WIN 55,512-2 biased animals to select the response lever conditioned for denser reinforcement. The same two drugs rendered peculiar response patterns in distracter light session components, considering light blinks were included to divert subjects’ attention away from task-relevant information. The response patterns determined during distracter components of PCP/WIN testing sessions, counterintuitively, suggest performance enhancement. Conclusion Comprehensive viewing of RD performance patterns after drug administration indicates that sustained attention and transient information management are significantly impaired during the drug-induced psychosis state, while selective attention is less affected.

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Site-Selective N-Methyl-?-Aspartate and α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionate Antagonists Produce Distinct Effects in Rats Performing Complex Discriminations

Cited by 8 publications

References 92 publications

Coantagonism of glutamate receptors and nicotinic acetylcholinergic receptors disrupts fear conditioning and latent inhibition of fear conditioning

Coantagonism of glutamate receptors and nicotinic acetylcholinergic receptors disrupts fear conditioning and latent inhibition of fear conditioning

Deficit of NMDA receptor activation in CA1 hippocampal area of aged rats is rescued by d‐cycloserine

Cognitive effects of psychotomimetic drugs in rats discriminating number cues

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