D-Cycloserine reverses the working memory impairment of hippocampal-lesioned rats in a spatial learning task

Schuster, G.; Schmidt, Werner

doi:10.1016/0014-2999(92)94825-g

Cited by 92 publications

(31 citation statements)

References 5 publications

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“…DCS has promnestic effects in rodents (Land and Riccio 1999;Pussinen and Sirvio 1999). It reverses memory deficits after anticholinergic treatment (Ohno and Watanabe 1996), and after septal (Riekkinen et al 1998) and hippocampal lesions (Schuster and Schmidt 1992). DCS also antagonizes aging-induced learning impairments (Baxter et al 1994) and was effective in combating cognitive deficits in Alzheimer patients (Tsai et al 1999).…”

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confidence: 96%

NMDA receptor modulation by d-cycloserine promotes episodic-like memory in mice

et al. 2007

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confidence: 96%

NMDA receptor modulation by d-cycloserine promotes episodic-like memory in mice

et al. 2007

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“…From animal studies, an involvement of NMDA receptors in several aspects of cognitive function has been demonstrated. For example, NMDA antagonists may suppress long-term potentiation, a cellular analogue of learning, while the stimulation of NMDA receptors with partial agonists may reduce learning deficits in animal models of AD [2][3][4]. In addition, another study has demonstrated that an MK-801 blockade of NMDA receptors induces disseminated corticolimbic neuronal degeneration [5].…”

Section: Introductionmentioning

confidence: 99%

Association Analysis for the Genetic Variants of the NMDA Receptor Subunit 2b and Alzheimer’s Disease

Tsai

Liu²,

Liu³

et al. 2002

Dement Geriatr Cogn Disord

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N-methyl-D-aspartate (NMDA) receptor dysfunction has been implicated in the pathogenesis of Alzheimer’s disease (AD). The NMDA receptor is composed of several subunits, of which the receptor 2b subunit (NR2b) is of particular significance for AD. Abundant in the hippocampus of normal subjects, reductions in NR2b have been demonstrated in the hippocampus and entorhinal cortex of AD patients. In this study, we tested the hypothesis that the allelic variant (C2664T) of the NR2b confers susceptibility to AD using a sample population of 132 AD patients and 114 normal controls. The distribution of the NR2b genotypes (p = 0.600) and alleles (p = 0.652) did not differ significantly between AD patients and controls, however, suggesting that it is unlikely that the NR2b C2664T polymorphism plays a substantial role in conferring susceptibility to AD. We propose that other genetic variations of the NMDA subunits, relating either to AD or to the therapeutic response for NMDA partial agonists, may need further investigation.

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“…Low doses (1-30 mgkg) of D-cycloserine were effective in reducing impairments in place discrimination in a water maze (31,85) and spatial alternation in a T-maze (31) induced by scopolamine. D-Cycloserine also attenuated deficits in spatial learning caused by quinolinic acid lesions of the hippocampus (81). Taken together, these results suggest a possible role for D-cycloserine in treatment of cognitive disorders in humans, but the inferences that can be drawn from these data are limited by the models available to test D-cycloserine.…”

Section: Effects On Learning and Memorymentioning

confidence: 93%

Modulation of the NMDA Receptor Complex by D‐Cycloserine

Baxter

Lanthorn

1995

CNS Drug Reviews

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D-Cyclosenne (~-4-amino-3-isoxazohdone)is an antibiotic that has primarily been used for tuberculosis therapy and acts by inhibiting bacterial cell wall synthesis (57). In addition to this tuberculostatic activity, D-cycloserine possesses partial agonist activity at the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptor, resulting in a variety of central nervous system effects independent of its antibiotic character.The NMDA receptor is a ligand-gated ion channel which is permeable to calcium as well as to monovalent cations. It has a number of modulatory sites in addition to the agonist (glutamate)-binding site, including a strychnine-insensitive glycine site, a polyamine modulatory site, and a PCP/dizocilpine-binding site (60, 83). Direct agonists of the glutamate receptor produce a wide variety of deleterious effects including seizures and neurotoxicity (59). Modulators of the NMDA receptor-associated glycine site are a more attractive option for enhancing the function of the NMDA receptor than are NMDA agonists, as they should lack the toxic properties of direct agonists. Occupancy of the glycine site is required for activation of the NMDA receptor channel (47). D-Cycloserine is a compound that acts as a partial agonist at the glycine site. In the absence of glycine, D-CyClOSerine potentiates NMDA-mediated synaptic responses, but in the presence of glycine D-cycloserine can reduce these responses (38, 61,92).The NMDA receptor is involved in a wide range of neurobiological processes including memory formation, neurodegeneration, seizure activity, and psychosis. D-CYcloserine, along with related partial agonists of the NMDA receptor-associated glycine site, possesses a more complex in vivo pharmacology than simple partial agonist activity. We will briefly discuss the pharmacokinetics and pharmacology of D-cyclo-

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D-Cycloserine reverses the working memory impairment of hippocampal-lesioned rats in a spatial learning task

Cited by 92 publications

References 5 publications

NMDA receptor modulation by d-cycloserine promotes episodic-like memory in mice

NMDA receptor modulation by d-cycloserine promotes episodic-like memory in mice

Association Analysis for the Genetic Variants of the NMDA Receptor Subunit 2b and Alzheimer’s Disease

Modulation of the NMDA Receptor Complex by D‐Cycloserine

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