Acute but not chronic activation of the NMDA-coupled glycine receptor with D-cycloserine facilitates learning and retention
Abstract
The memory-enhancing potential of D-cycloserine (cycloserine) a partial agonist at the glycine recognition site on the NMDA receptor, was evaluated in mice using a thirst-motivated linear maze learning task. Immediate acute post-training injections (10, 20 and 80 mg/kg) significantly improved retention relative to vehicle-injected controls. Retention was also facilitated if cycloserine (3 and 10 mg/kg but not 20 or 40 mg/kg) was administered 20 min before the retention test. Acquisition of the habit was accelerated if cycloserine (3 mg/kg) was injected 20 min before the training session. Acute post-training injections failed to facilitate retention if mice were pretreated with cycloserine (3 mg/kg) b.i.d. for 15 days before training on the maze. These results indicate that acute cycloserine administration can enhance consolidation and retrieval of memory but that desensitization may occur with chronic exposure to the drug.
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Daily, longer-term dosing appears to reduce the cognitive enhancing effects of DCS.
“and because daily, longer-term dosing appears to reduce the cognitive enhancing effects of DCS (Quartermain et al, 1994), possibly due to desensitization of the NMDA receptor over time (Boje et al, 1993).”
From D-cycloserine augmentation of exposure therapy for post-traumatic stress disorder: a pilot randomized clinical trial (2014) · cites this paper as Quartermain et al, 1994
Studies by Parnas et al (2005) and Quartermain et al (1994) described multiple administration of DCS before fear conditioning or the maze learning test, respectively.
“Studies reported by Parnas et al (2005) and Quartermain et al (1994) described the multiple administration of DCS before fear conditioning or the maze learning test, respectively (ie preadministration of DCS).”
From Effects of Single Prolonged Stress and D-Cycloserine on Contextual Fear Extinction and Hippocampal NMDA Receptor Expression in a Rat Model of PTSD (2008) · cites this paper as Quartermain et al (1994)
Chronic preexposure to DCS for 15 days led to a significant decrease in the effect of DCS upon the maze learning test.
“Similarly, Quartermain et al (1994) reported that chronic preexposure to DCS for 15 days led to a significant decrease in the effect of DCS upon the maze learning test (Quartermain et al, 1994).”
From Effects of Single Prolonged Stress and D-Cycloserine on Contextual Fear Extinction and Hippocampal NMDA Receptor Expression in a Rat Model of PTSD (2008) · cites this paper as Quartermain et al (1994)
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- Authors
- Quartermain, D., Mower, J., Rafferty, M. F., Herting, R. L., & Lanthorn, T. H.
- Affiliations
- NYU Langone Health (US)
- Corresponding author
- Quartermain, David
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 1994-05
- Volume
- 257
- Issue
- 1-2
- Pages
- 7-12
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W1989766588
- Cited by
- 190
- References
- 26
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 12 · 2022: 4 · 2021: 2 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 9 · 2016: 4 · 2015: 8 · 2014: 12 · 2013: 10 · 2012: 10
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- D-cycloserine, NMDA receptor, glycine receptor, partial agonists, memory enhancement, learning and retention, memory consolidation, memory retrieval, desensitization, chronic drug exposure, acute drug administration
- MeSH terms
- Analysis of Variance, Animals, Behavior, Animal, Cycloserine, Drug Administration Schedule, Learning, Male, Memory, Receptors, N-Methyl-D-Aspartate, Receptors, Glycine, Mice
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