D-Cycloserine in Neuropsychiatric Diseases: A Systematic Review

Schade, Sebastian; Paulus, Walter

doi:10.1093/ijnp/pyv102

Cited by 99 publications

(80 citation statements)

References 73 publications

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“…Thus, increasing NMDAR function during extinction training, e.g. with d ‐serine or the partial agonist d ‐cycloserine, could increase extinction learning and reduce the ability of intoxicant‐related cues to drive addictive behaviors (Myers et al ; Myers & Carlezon ; Hammond et al ; Schade & Paulus ). In humans, pairing d ‐cycloserine with extinction of alcohol cues decreases cue‐induced activation of dorsal and ventral striatum, where decreased cue‐related brain activation correlates with lower craving and relapse risk (Kiefer et al ).…”

Section: Plasticity and Contributions Of Nmdar Co‐agonistsmentioning

confidence: 99%

Do specific NMDA receptor subunits act as gateways for addictive behaviors?

Hopf

2016

Genes Brain and Behavior

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Addiction to alcohol and drugs is a major social and economic problem, and there is considerable interest in understanding the molecular mechanisms that promote addictive drives. A number of proteins have been identified that contribute to expression of addictive behaviors. NMDA receptors (NMDARs), a subclass of ionotropic glutamate receptors, have been of particular interest because their physiological properties make them an attractive candidate for gating induction of synaptic plasticity, a molecular change thought to mediate learning and memory. NMDARs are generally inactive at the hyperpolarized resting potentials of many neurons. However, given sufficient depolarization, NMDARs are activated and exhibit long-lasting currents with significant calcium permeability. Also, in addition to stimulating neurons by direct depolarization, NMDARs and their calcium signaling can allow strong and/or synchronized inputs to produce long-term changes in other molecules (such as AMPA-type glutamate receptors) which can last from days to years, binding internal and external stimuli in a long-term memory trace. Such memories could allow salient drug-related stimuli to exert strong control over future behaviors and thus promote addictive drives. Finally, NMDARs may themselves undergo plasticity, which can alter subsequent neuronal stimulation and/or the ability to induce plasticity. This review will address recent and past findings suggesting that NMDAR activity promotes drug- and alcohol-related behaviors, with a particular focus on GluN2B subunits as possible central regulators of many addictive behaviors, as well as newer studies examining the importance of non-canonical NMDAR subunits and endogenous NMDAR cofactors.

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Section: Plasticity and Contributions Of Nmdar Co‐agonistsmentioning

confidence: 99%

Do specific NMDA receptor subunits act as gateways for addictive behaviors?

Hopf

2016

Genes Brain and Behavior

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“…Evidence for reduced excitatory neurotransmission, long‐term potentiation, NMDA/AMPA ratio, and dendritic spine abnormalities in Shank3B mice formed the basis of our hypothesis that pharmacologically increasing glutamatergic neurotransmission could improve social behaviors and/or reduce repetitive behaviors in Shank3B . To investigate the possibility that enhancing glutamatergic synaptic transmission and increasing glutamatergic excitation could reverse autism‐relevant phenotypes in Shank3B mice [Lovinger, ; Wang et al, ], three classes of pharmacological compounds were evaluated in Shank3B and their wildtype littermate controls: (a) a partial agonist at the glycine modulatory site on the NMDA receptor, d‐cycloserine, that has been evaluated preclinically and in clinical trials for several neuropsychiatric disorders [Baxter et al, ; Myers & Carlezon, ; Schade & Paulus, ]; (b) an Ampakine positive allosteric modulator of the glutamatergic AMPA receptor, CX546, one of a class of compounds found to improve cognition in rodents and tested in clinical trials for schizophrenia and Fragile X syndrome [Goff et al, ; Berry‐Kravis et al, ; Arai & Kessler, ; Lynch, Palmer, & Gall, ]; and (c) the TrkB agonist 7,8‐DHF, as described above. Two behavioral assays in which Shank3B mice were previously reported to display robust and replicated deficits were employed as outcome measures, male–female reciprocal social interactions and repetitive self‐grooming, along with open field exploratory locomotion as a control for the potential confounds of sedation and hyperactivity after drug treatments.…”

Section: Resultsmentioning

confidence: 99%

Hypothesis‐driven investigations of diverse pharmacological targets in two mouse models of autism

et al. 2019

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Autism spectrum disorder is a neurodevelopmental syndrome diagnosed primarily by persistent deficits in social interactions and communication, unusual sensory reactivity, motor stereotypies, repetitive behaviors, and restricted interests. No FDA‐approved medical treatments exist for the diagnostic symptoms of autism. Here we interrogate multiple pharmacological targets in two distinct mouse models that incorporate well‐replicated autism‐relevant behavioral phenotypes. Compounds that modify inhibitory or excitatory neurotransmission were selected to address hypotheses based on previously published biological abnormalities in each model. Shank3B is a genetic model of a mutation found in autism and Phelan‐McDermid syndrome, in which deficits in excitatory neurotransmission and synaptic plasticity have been reported. BTBR is an inbred strain model of forms of idiopathic autism in which reduced inhibitory neurotransmission and excessive mTOR signaling have been reported. The GABA‐A receptor agonist gaboxadol significantly reduced repetitive self‐grooming in three independent cohorts of BTBR. The TrkB receptor agonist 7,8‐DHF improved spatial learning in Shank3B mice, and reversed aspects of social deficits in BTBR. CX546, a positive allosteric modulator of the glutamatergic AMPA receptor, and d‐cycloserine, a partial agonist of the glycine site on the glutamatergic NMDA receptor, did not rescue aberrant behaviors in Shank3B mice. The mTOR inhibitor rapamycin did not ameliorate social deficits or repetitive behavior in BTBR mice. Comparison of positive and negative pharmacological outcomes, on multiple phenotypes, evaluated for replicability across independent cohorts, enhances the translational value of mouse models of autism for therapeutic discovery. GABA agonists present opportunities for personalized interventions to treat components of autism spectrum disorder. Autism Res 2019, 12: 401–421 © 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. Lay Summary Many of the risk genes for autism impair synapses, the connections between nerve cells in the brain. A drug that reverses the synaptic effects of a mutation could offer a precision therapy. Combining pharmacological and behavioral therapies could reduce symptoms and improve the quality of life for people with autism. Here we report reductions in repetitive behavior by a GABA‐A receptor agonist, gaboxadol, and improvements in social and cognitive behaviors by a TrkB receptor agonist, in mouse models of autism.

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“…Cycloserine targets the glycine-binding site of Nmethyl-D-aspartate (NMDA) receptors in humans. Altogether, Cycloserine seems to have an impact on cognitive functions, mainly those associated with NMDA receptor-dependent mechanisms like long-term potentiation in learning processes [17].…”

Section: Discussionmentioning

confidence: 99%

Influence social and healthcare support on psychiatric adverse events in MDR-TB patient

Reviono

Harsini

Aphridasari

et al. 2018

J Infect Dev Ctries

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Introduction: Multidrug resistance tuberculosis (MDR-TB) is a continuing threat because the treatment is rather toxic. One of the causes of poor treatment outcome is due to the adverse events, especially the occurrence of psychiatric adverse events. Methodology: The two cases presented in this paper are MDR-TB patients with psychiatric adverse events related to depression spectrum. The diagnosis of psychiatric adverse events was done by psychiatrist in the referral hospital. Results: The treatment of MDR-TB and psychiatric adverse event was carried out simultaneously. One of the patients was able to manage the adverse events, but the other was not. The management of psychiatric adverse events need to be performed carefully. Social support of family and friends was received by the successful patient, while the other was not fully supported, thus failed the treatment. Conclusion: The social support provided by the family and friends are precious for the successful treatment of MDR-TB psychiatric adverse events. The availability of healthcare personnel who is able to recognize the symptoms early is needed in the community healthcare service in order to properly detect and manage the psychiatric adverse events on MDR-TB patients.

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D-Cycloserine in Neuropsychiatric Diseases: A Systematic Review

Cited by 99 publications

References 73 publications

Do specific NMDA receptor subunits act as gateways for addictive behaviors?

Do specific NMDA receptor subunits act as gateways for addictive behaviors?

Hypothesis‐driven investigations of diverse pharmacological targets in two mouse models of autism

Influence social and healthcare support on psychiatric adverse events in MDR-TB patient

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