D-Serín

Pôsobí na: mozog a kognitívne funkcie

D-Serín je aminokyselina, ktorá zohráva úlohu pri zlepšovaní poznávacích funkcií a liečbe schizofrénie.

Užívanie

Bežná dávka je 30 mg/kg telesnej hmotnosti. To približne zodpovedá dávke 2100 – 2700 mg pre 70-90 kg človeka. Zdá sa, že toto je minimálna účinná dávka na zlepšenie kognitívnych schopností u ľudí trpiacich rôznymi chorobami. Predbežné výskumy naznačujú, že dvoj- až štvornásobok tejto dávky prináša ďalšie výhody pre ľudí postihnutých schizofréniou.

Medicínske upozornenie!

Literatúra

  1. Martineau M, Baux G, Mothet JP. D-serine signalling in the brain: friend and foe. Trends Neurosci. (2006)
  2. Schell MJ. The N-methyl D-aspartate receptor glycine site and D-serine metabolism: an evolutionary perspective. Philos Trans R Soc Lond B Biol Sci. (2004)
  3. Monahan JB, et al. Characterization of a {3H}glycine recognition site as a modulatory site of the N-methyl-D-aspartate receptor complex. J Neurochem. (1989)
  4. D-serine, an endogenous synaptic modulator: localization to astrocytes and glutamate-stimulated release.
  5. Watson GB, et al. D-cycloserine acts as a partial agonist at the glycine modulatory site of the NMDA receptor expressed in Xenopus oocytes. Brain Res. (1990)
  6. Berger AJ, Dieudonné S, Ascher P. Glycine uptake governs glycine site occupancy at NMDA receptors of excitatory synapses. J Neurophysiol. (1998)
  7. Papouin T, et al. Synaptic and extrasynaptic NMDA receptors are gated by different endogenous coagonists. Cell. (2012)
  8. Radzishevsky I, Sason H, Wolosker H. D-serine: physiology and pathology. Curr Opin Clin Nutr Metab Care. (2013)
  9. Thomas CG, Miller AJ, Westbrook GL. Synaptic and extrasynaptic NMDA receptor NR2 subunits in cultured hippocampal neurons. J Neurophysiol. (2006)
  10. Groc L, et al. NMDA receptor surface mobility depends on NR2A-2B subunits. Proc Natl Acad Sci U S A. (2006)
  11. Martel MA, et al. The subtype of GluN2 C-terminal domain determines the response to excitotoxic insults. Neuron. (2012)
  12. Yasuda E, Ma N, Semba R. Immunohistochemical evidences for localization and production of D-serine in some neurons in the rat brain. Neurosci Lett. (2001)
  13. Yang Y, et al. Contribution of astrocytes to hippocampal long-term potentiation through release of D-serine. Proc Natl Acad Sci U S A. (2003)
  14. Wolosker H, Blackshaw S, Snyder SH. Serine racemase: a glial enzyme synthesizing D-serine to regulate glutamate-N-methyl-D-aspartate neurotransmission. Proc Natl Acad Sci U S A. (1999)
  15. Xia M, et al. Characterization and localization of a human serine racemase. Brain Res Mol Brain Res. (2004)
  16. Williams SM, et al. Immunocytochemical analysis of D-serine distribution in the mammalian brain reveals novel anatomical compartmentalizations in glia and neurons. Glia. (2006)
  17. De Miranda J, et al. Cofactors of serine racemase that physiologically stimulate the synthesis of the N-methyl-D-aspartate (NMDA) receptor coagonist D-serine. Proc Natl Acad Sci U S A. (2002)
  18. Neidle A, Dunlop DS. Allosteric regulation of mouse brain serine racemase. Neurochem Res. (2002)
  19. Cook SP, et al. Direct calcium binding results in activation of brain serine racemase. J Biol Chem. (2002)
  20. Strísovský K, et al. Dual substrate and reaction specificity in mouse serine racemase: identification of high-affinity dicarboxylate substrate and inhibitors and analysis of the beta-eliminase activity. Biochemistry. (2005)
  21. Dunlop DS, Neidle A. Regulation of serine racemase activity by amino acids. Brain Res Mol Brain Res. (2005)
  22. Kim PM, et al. Serine racemase: activation by glutamate neurotransmission via glutamate receptor interacting protein and mediation of neuronal migration. Proc Natl Acad Sci U S A. (2005)
  23. Strísovský K, et al. Mouse brain serine racemase catalyzes specific elimination of L-serine to pyruvate. FEBS Lett. (2003)
  24. Urai Y, et al. Gene expression of D-amino acid oxidase in cultured rat astrocytes: regional and cell type specific expression. Neurosci Lett. (2002)
  25. Molla G, et al. Characterization of human D-amino acid oxidase. FEBS Lett. (2006)
  26. Horiike K, et al. D-amino-acid oxidase is confined to the lower brain stem and cerebellum in rat brain: regional differentiation of astrocytes. Brain Res. (1994)
  27. Moreno S, et al. Immunocytochemical localization of D-amino acid oxidase in rat brain. J Neurocytol. (1999)
  28. Hamase K, et al. Sensitive determination of D-amino acids in mammals and the effect of D-amino-acid oxidase activity on their amounts. Biol Pharm Bull. (2005)
  29. Heresco-Levy U, et al. D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia. Biol Psychiatry. (2005)
  30. Heresco-Levy U, et al. High-dose glycine added to olanzapine and risperidone for the treatment of schizophrenia. Biol Psychiatry. (2004)
  31. Lane HY, et al. A randomized, double-blind, placebo-controlled comparison study of sarcosine (N-methylglycine) and D-serine add-on treatment for schizophrenia. Int J Neuropsychopharmacol. (2010)
  32. Lane HY, et al. Sarcosine or D-serine add-on treatment for acute exacerbation of schizophrenia: a randomized, double-blind, placebo-controlled study. Arch Gen Psychiatry. (2005)
  33. Kantrowitz JT, et al. High dose D-serine in the treatment of schizophrenia. Schizophr Res. (2010)
  34. Gelfin E, et al. D-serine adjuvant treatment alleviates behavioural and motor symptoms in Parkinson’s disease. Int J Neuropsychopharmacol. (2012)
  35. Heresco-Levy U, et al. Pilot controlled trial of D-serine for the treatment of post-traumatic stress disorder. Int J Neuropsychopharmacol. (2009)
  36. Nagata Y, et al. Free D-serine concentration in normal and Alzheimer human brain. Brain Res Bull. (1995)
  37. Chouinard ML, Gaitan D, Wood PL. Presence of the N-methyl-D-aspartate-associated glycine receptor agonist, D-serine, in human temporal cortex: comparison of normal, Parkinson, and Alzheimer tissues. J Neurochem. (1993)
  38. Kumashiro S, Hashimoto A, Nishikawa T. Free D-serine in post-mortem brains and spinal cords of individuals with and without neuropsychiatric diseases. Brain Res. (1995)
  39. Foltyn VN, et al. Serine racemase modulates intracellular D-serine levels through an alpha,beta-elimination activity. J Biol Chem. (2005)
  40. Otte DM, et al. Effects of Chronic D-Serine Elevation on Animal Models of Depression and Anxiety-Related Behavior. PLoS One. (2013)
  41. Sethuraman R, et al. Simultaneous analysis of D- and L-serine in cerebrospinal fluid by use of HPLC. Clin Chem. (2007)
  42. Hashimoto K, et al. Reduced D-serine to total serine ratio in the cerebrospinal fluid of drug naive schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry. (2005)
  43. Bezzi P, et al. Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate. Nat Neurosci. (2004)
  44. Mothet JP, et al. Glutamate receptor activation triggers a calcium-dependent and SNARE protein-dependent release of the gliotransmitter D-serine. Proc Natl Acad Sci U S A. (2005)
  45. Schell MJ, et al. D-serine as a neuromodulator: regional and developmental localizations in rat brain glia resemble NMDA receptors. J Neurosci. (1997)
  46. Van Horn MR, Sild M, Ruthazer ES. D-serine as a gliotransmitter and its roles in brain development and disease. Front Cell Neurosci. (2013)
  47. Sild M, Van Horn MR. Astrocytes use a novel transporter to fill gliotransmitter vesicles with d-serine: evidence for vesicular synergy. J Neurosci. (2013)
  48. Bergersen LH, et al. Immunogold detection of L-glutamate and D-serine in small synaptic-like microvesicles in adult hippocampal astrocytes. Cereb Cortex. (2012)
  49. Storage and Uptake of D-Serine into Astrocytic Synaptic-Like Vesicles Specify Gliotransmission.
  50. Rosenberg D, et al. Neuronal release of D-serine: a physiological pathway controlling extracellular D-serine concentration. FASEB J. (2010)
  51. Rosenberg D, et al. Neuronal D-serine and glycine release via the Asc-1 transporter regulates NMDA receptor-dependent synaptic activity. J Neurosci. (2013)
  52. Kang N, et al. Astrocytes release D-serine by a large vesicle. Neuroscience. (2013)
  53. Shigetomi E, et al. TRPA1 Channels Are Regulators of Astrocyte Basal Calcium Levels and Long-Term Potentiation via Constitutive D-Serine Release. J Neurosci. (2013)
  54. Long term potentiation depends on release of D-serine from astrocytes.
  55. Shoji K, et al. Regulation of serine racemase activity by D-serine and nitric oxide in human glioblastoma cells. Neurosci Lett. (2006)
  56. Shoji K, et al. Mutual regulation between serine and nitric oxide metabolism in human glioblastoma cells. Neurosci Lett. (2006)
  57. Alagarsamy S, Johnson KM. Voltage-dependent calcium channel involvement in NMDA-induced activation of NOS. Neuroreport. (1995)
  58. Bado P, et al. Effects of low-dose D-serine on recognition and working memory in mice. Psychopharmacology (Berl). (2011)
  59. Chen L, Muhlhauser M, Yang CR. Glycine tranporter-1 blockade potentiates NMDA-mediated responses in rat prefrontal cortical neurons in vitro and in vivo. J Neurophysiol. (2003)
  60. Lim R, Hoang P, Berger AJ. Blockade of glycine transporter-1 (GLYT-1) potentiates NMDA receptor-mediated synaptic transmission in hypoglossal motorneurons. J Neurophysiol. (2004)
  61. Hashimoto A, et al. The presence of free D-serine in rat brain. FEBS Lett. (1992)
  62. Endogenous d-Serine in Rat Brain: N-Methyl-d-Aspartate Receptor-Related Distribution and Aging.
  63. Johnson JW, Ascher P. Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature. (1987)
  64. Clements JD, Westbrook GL. Activation kinetics reveal the number of glutamate and glycine binding sites on the N-methyl-D-aspartate receptor. Neuron. (1991)
  65. Kalia LV, Kalia SK, Salter MW. NMDA receptors in clinical neurology: excitatory times ahead. Lancet Neurol. (2008)
  66. Mothet JP, et al. D-serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor. Proc Natl Acad Sci U S A. (2000)
  67. Supplisson S, Bergman C. Control of NMDA receptor activation by a glycine transporter co-expressed in Xenopus oocytes. J Neurosci. (1997)
  68. Wilcox KS, et al. Glycine regulation of synaptic NMDA receptors in hippocampal neurons. J Neurophysiol. (1996)
  69. Depoortère R, et al. Neurochemical, electrophysiological and pharmacological profiles of the selective inhibitor of the glycine transporter-1 SSR504734, a potential new type of antipsychotic. Neuropsychopharmacology. (2005)
  70. Martina M, Krasteniakov NV, Bergeron R. D-Serine differently modulates NMDA receptor function in rat CA1 hippocampal pyramidal cells and interneurons. J Physiol. (2003)
  71. Thomson AM, Walker VE, Flynn DM. Glycine enhances NMDA-receptor mediated synaptic potentials in neocortical slices. Nature. (1989)
  72. Stevens ER, et al. D-serine and serine racemase are present in the vertebrate retina and contribute to the physiological activation of NMDA receptors. Proc Natl Acad Sci U S A. (2003)
  73. Gong XQ, Zabek RL, Bai D. D-Serine inhibits AMPA receptor-mediated current in rat hippocampal neurons. Can J Physiol Pharmacol. (2007)
  74. McNamara D, Dingledine R. Dual effect of glycine on NMDA-induced neurotoxicity in rat cortical cultures. J Neurosci. (1990)
  75. The glycinergic inhibitory synapse.
  76. Betz H, et al. Glycine transporters: essential regulators of synaptic transmission. Biochem Soc Trans. (2006)
  77. Aragón C, López-Corcuera B. Glycine transporters: crucial roles of pharmacological interest revealed by gene deletion. Trends Pharmacol Sci. (2005)
  78. Hayashi F, Takahashi K, Nishikawa T. Uptake of D- and L-serine in C6 glioma cells. Neurosci Lett. (1997)
  79. Ribeiro CS, et al. Glial transport of the neuromodulator D-serine. Brain Res. (2002)
  80. Coyle JT, Puttfarcken P. Oxidative stress, glutamate, and neurodegenerative disorders. Science. (1993)
  81. Armagan G, Kanit L, Yalcin A. Effects of non-steroidal antiinflammatory drugs on D-serine-induced oxidative stress in vitro. Drug Chem Toxicol. (2012)
  82. Armagan G, Kanit L, Yalcin A. D-serine treatment induces oxidative stress in rat brain. Drug Chem Toxicol. (2011)
  83. Leipnitz G, et al. d-Serine administration provokes lipid oxidation and decreases the antioxidant defenses in rat striatum. Int J Dev Neurosci. (2010)
  84. Kinouchi H, et al. Induction of cyclooxygenase-2 messenger RNA after transient and permanent middle cerebral artery occlusion in rats: comparison with c-fos messenger RNA by using in situ hybridization. J Neurosurg. (1999)
  85. Collaço-Moraes Y, et al. Cyclo-oxygenase-2 messenger RNA induction in focal cerebral ischemia. J Cereb Blood Flow Metab. (1996)
  86. Dash PK, Mach SA, Moore AN. Regional expression and role of cyclooxygenase-2 following experimental traumatic brain injury. J Neurotrauma. (2000)
  87. Pasinetti GM. Cyclooxygenase and inflammation in Alzheimer’s disease: experimental approaches and clinical interventions. J Neurosci Res. (1998)
  88. Hewett SJ, et al. Cyclooxygenase-2 contributes to N-methyl-D-aspartate-mediated neuronal cell death in primary cortical cell culture. J Pharmacol Exp Ther. (2000)
  89. Silva AJ. Molecular and cellular cognitive studies of the role of synaptic plasticity in memory. J Neurobiol. (2003)
  90. Matynia A, Kushner SA, Silva AJ. Genetic approaches to molecular and cellular cognition: a focus on LTP and learning and memory. Annu Rev Genet. (2002)
  91. Tang YP, et al. Genetic enhancement of learning and memory in mice. Nature. (1999)
  92. Hawasli AH, et al. Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation. Nat Neurosci. (2007)
  93. Panatier A, et al. Glia-derived D-serine controls NMDA receptor activity and synaptic memory. Cell. (2006)
  94. Braunewell KH, Manahan-Vaughan D. Long-term depression: a cellular basis for learning. Rev Neurosci. (2001)
  95. Duffy S, Labrie V, Roder JC. D-serine augments NMDA-NR2B receptor-dependent hippocampal long-term depression and spatial reversal learning. Neuropsychopharmacology. (2008)
  96. Zhang Z, et al. Bell-shaped D-serine actions on hippocampal long-term depression and spatial memory retrieval. Cereb Cortex. (2008)
  97. Landfield PW, Pitler TA, Applegate MD. The effects of high Mg2+-to-Ca2+ ratios on frequency potentiation in hippocampal slices of young and aged rats. J Neurophysiol. (1986)
  98. Landfield PW, Lynch G. Impaired monosynaptic potentiation in in vitro hippocampal slices from aged, memory-deficient rats. J Gerontol. (1977)
  99. Foster TC. Calcium homeostasis and modulation of synaptic plasticity in the aged brain. Aging Cell. (2007)
  100. Thibault O, Gant JC, Landfield PW. Expansion of the calcium hypothesis of brain aging and Alzheimer’s disease: minding the store. Aging Cell. (2007)
  101. Billard JM. Serine racemase as a prime target for age-related memory deficits. Eur J Neurosci. (2013)
  102. Turpin FR, et al. Reduced serine racemase expression contributes to age-related deficits in hippocampal cognitive function. Neurobiol Aging. (2011)
  103. Magnusson KR, Nelson SE, Young AB. Age-related changes in the protein expression of subunits of the NMDA receptor. Brain Res Mol Brain Res. (2002)
  104. Adams MM, et al. Hippocampal dependent learning ability correlates with N-methyl-D-aspartate (NMDA) receptor levels in CA3 neurons of young and aged rats. J Comp Neurol. (2001)
  105. Alliot J, et al. The LOU/c/jall rat as an animal model of healthy aging. J Gerontol A Biol Sci Med Sci. (2002)
  106. Mothet JP, et al. A critical role for the glial-derived neuromodulator D-serine in the age-related deficits of cellular mechanisms of learning and memory. Aging Cell. (2006)
  107. Junjaud G, et al. Age-related effects of the neuromodulator D-serine on neurotransmission and synaptic potentiation in the CA1 hippocampal area of the rat. J Neurochem. (2006)
  108. Long term potentiation depends on release of D-serine from astrocytes.
  109. Assini FL, Duzzioni M, Takahashi RN. Object location memory in mice: pharmacological validation and further evidence of hippocampal CA1 participation. Behav Brain Res. (2009)
  110. Zlomuzica A, et al. NMDA receptor modulation by D-cycloserine promotes episodic-like memory in mice. Psychopharmacology (Berl). (2007)
  111. Levin R1, et al. Behavioral and cognitive effects of the N-methyl-d-aspartate receptor co-agonist d-serine in healthy humans: Initial findings. J Psychiatr Res. (2014)
  112. Lipton SA, Rosenberg PA. Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med. (1994)
  113. Farber NB, Newcomer JW, Olney JW. The glutamate synapse in neuropsychiatric disorders. Focus on schizophrenia and Alzheimer’s disease. Prog Brain Res. (1998)
  114. Paula-Lima AC, Brito-Moreira J, Ferreira ST. Deregulation of excitatory neurotransmission underlying synapse failure in Alzheimer’s disease. J Neurochem. (2013)
  115. Huang YJ, et al. NMDA Neurotransmission Dysfunction in Behavioral and Psychological Symptoms of Alzheimer’s Disease. Curr Neuropharmacol. (2012)
  116. Brito-Moreira J, et al. Aβ oligomers induce glutamate release from hippocampal neurons. Curr Alzheimer Res. (2011)
  117. Wu S, Basile AS, Barger SW. Induction of serine racemase expression and D-serine release from microglia by secreted amyloid precursor protein (sAPP). Curr Alzheimer Res. (2007)
  118. Wu SZ, et al. Induction of serine racemase expression and D-serine release from microglia by amyloid beta-peptide. J Neuroinflammation. (2004)
  119. Nunes EA, et al. D-serine and schizophrenia: an update. Expert Rev Neurother. (2012)
  120. Labrie V, Roder JC. The involvement of the NMDA receptor D-serine/glycine site in the pathophysiology and treatment of schizophrenia. Neurosci Biobehav Rev. (2010)
  121. Waziri R, Baruah S, Sherman AD. Abnormal serine-glycine metabolism in the brains of schizophrenics. Schizophr Res. (1993)
  122. Waziri R, et al. Abnormal serine hydroxymethyl transferase activity in the temporal lobes of schizophrenics. Neurosci Lett. (1990)
  123. Hashimoto K, et al. Decreased serum levels of D-serine in patients with schizophrenia: evidence in support of the N-methyl-D-aspartate receptor hypofunction hypothesis of schizophrenia. Arch Gen Psychiatry. (2003)
  124. Hashimoto K. Glycine transport inhibitors for the treatment of schizophrenia. Open Med Chem J. (2010)
  125. Dysfunction of Glia-Neuron Communication in Pathophysiology of Schizophrenia.
  126. Labrie V, Lipina T, Roder JC. Mice with reduced NMDA receptor glycine affinity model some of the negative and cognitive symptoms of schizophrenia. Psychopharmacology (Berl). (2008)
  127. Balu DT, et al. Multiple risk pathways for schizophrenia converge in serine racemase knockout mice, a mouse model of NMDA receptor hypofunction. Proc Natl Acad Sci U S A. (2013)
  128. Ma TM, et al. Pathogenic disruption of DISC1-serine racemase binding elicits schizophrenia-like behavior via D-serine depletion. Mol Psychiatry. (2013)
  129. Labrie V, et al. Genetic loss of D-amino acid oxidase activity reverses schizophrenia-like phenotypes in mice. Genes Brain Behav. (2010)
  130. Ohnuma T, et al. Changes in plasma glycine, L-serine, and D-serine levels in patients with schizophrenia as their clinical symptoms improve: results from the Juntendo University Schizophrenia Projects (JUSP). Prog Neuropsychopharmacol Biol Psychiatry. (2008)
  131. Buchanan RW. Novel pharmacologic targets for the treatment of negative symptoms in schizophrenia. J Clin Psychiatry. (2013)
  132. Tsai G, et al. Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry. (2004)
  133. Dingledine R, et al. The glutamate receptor ion channels. Pharmacol Rev. (1999)
  134. Traynelis SF, et al. Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev. (2010)
  135. Lewis DA, Gonzalez-Burgos G. Pathophysiologically based treatment interventions in schizophrenia. Nat Med. (2006)
  136. Ross CA, et al. Neurobiology of schizophrenia. Neuron. (2006)
  137. Tsai G, et al. D-serine added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry. (1998)
  138. Weiser M, et al. A multicenter, add-on randomized controlled trial of low-dose d-serine for negative and cognitive symptoms of schizophrenia. J Clin Psychiatry. (2012)
  139. Tsai GE, et al. D-serine added to clozapine for the treatment of schizophrenia. Am J Psychiatry. (1999)
  140. Isella V, et al. Clinical, neuropsychological, and morphometric correlates of apathy in Parkinson’s disease. Mov Disord. (2002)
  141. Pluck GC, Brown RG. Apathy in Parkinson’s disease. J Neurol Neurosurg Psychiatry. (2002)
  142. Chéramy A, et al. Direct and indirect presynaptic control of dopamine release by excitatory amino acids. Amino Acids. (1998)
  143. Hallett PJ, Standaert DG. Rationale for and use of NMDA receptor antagonists in Parkinson’s disease. Pharmacol Ther. (2004)
  144. Chambers RA, et al. Glutamate and post-traumatic stress disorder: toward a psychobiology of dissociation. Semin Clin Neuropsychiatry. (1999)
  145. Newcomer JW, Krystal JH. NMDA receptor regulation of memory and behavior in humans. Hippocampus. (2001)
  146. Heresco-Levy U, et al. Pilot-controlled trial of D-cycloserine for the treatment of post-traumatic stress disorder. Int J Neuropsychopharmacol. (2002)
  147. Sasabe J, et al. D-serine is a key determinant of glutamate toxicity in amyotrophic lateral sclerosis. EMBO J. (2007)
  148. Thompson M, et al. Paradoxical roles of serine racemase and D-serine in the G93A mSOD1 mouse model of amyotrophic lateral sclerosis. J Neurochem. (2012)
  149. Crow JP, Marecki JC, Thompson M. D-Serine Production, Degradation, and Transport in ALS: Critical Role of Methodology. Neurol Res Int. (2012)
  150. Lüscher C, Malenka RC. Drug-evoked synaptic plasticity in addiction: from molecular changes to circuit remodeling. Neuron. (2011)
  151. Kauer JA, Malenka RC. Synaptic plasticity and addiction. Nat Rev Neurosci. (2007)
  152. Transition to Addiction Is Associated with a Persistent Impairment in Synaptic Plasticity.
  153. Martin M, et al. Cocaine self-administration selectively abolishes LTD in the core of the nucleus accumbens. Nat Neurosci. (2006)
  154. Moussawi K, et al. N-Acetylcysteine reverses cocaine-induced metaplasticity. Nat Neurosci. (2009)
  155. Curcio L, et al. Reduced D-serine levels in the nucleus accumbens of cocaine-treated rats hinder the induction of NMDA receptor-dependent synaptic plasticity. Brain. (2013)
  156. Kelamangalath L, Seymour CM, Wagner JJ. D-serine facilitates the effects of extinction to reduce cocaine-primed reinstatement of drug-seeking behavior. Neurobiol Learn Mem. (2009)
  157. Kelamangalath L, Wagner JJ. D-serine treatment reduces cocaine-primed reinstatement in rats following extended access to cocaine self-administration. Neuroscience. (2010)
  158. Hammond S, et al. D-Serine facilitates the effectiveness of extinction to reduce drug-primed reinstatement of cocaine-induced conditioned place preference. Neuropharmacology. (2013)