ArticleThe international journal of neuropsychopharmacology2016
Combined Neuropeptide S and D-Cycloserine Augmentation Prevents the Return of Fear in Extinction-Impaired Rodents: Advantage of Dual versus Single Drug Approaches.
Article in The international journal of neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Neuropeptide S modulation of learning and memory: a systematic review.Behavioral and brain functions : BBF · 2026Pooled it
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- Sex-dependent role of hippocampal BDNF and GSK-3β in mediating PTSD-like behaviors in both sexes of adolescent rats exposed to fear conditioning, extinction, and reinstatement.Experimental brain research · 2025Article
- Synergistic behavioral and neuroplastic effects of psilocybin-NMDAR modulator administration.Translational psychiatry · 2025Article
- Ginkgo Biloba as a niche theme cognitive enhancer agent, 1420 dokumen of Scopus database. A bibliometric study from 1988 to 2024.F1000Research · 2025Article
- Fear extinction rescuing effects of dopamine and L-DOPA in the ventromedial prefrontal cortex.Translational psychiatry · 2024Article
- Synergistic psychedelic - NMDAR modulator treatment for neuropsychiatric disorders.Molecular psychiatry · 2024Article
- Role of the Neuropeptide S System in Emotionality, Stress Responsiveness and Addiction-Like Behaviours in Rodents: Relevance to Stress-Related Disorders.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Pharmacology, Physiology and Genetics of the Neuropeptide S System.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Turning strains into strengths for understanding psychiatric disorders.Molecular psychiatry · 2020Review
- Corticosterone Treatment and Incubation Time After Contextual Fear Conditioning Synergistically Induce Fear Memory Generalization in Neuropeptide S Receptor-Deficient Mice.Frontiers in neuroscience · 2020Article
- Rodent models of impaired fear extinction.Psychopharmacology · 2019Review
- Neuropeptide S Induces Acute Anxiolysis by Phospholipase C-Dependent Signaling within the Medial Amygdala.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Effects of systemic glutamatergic manipulations on conditioned eyeblink responses and hyperarousal in a rabbit model of post-traumatic stress disorder.Behavioural pharmacology · 2017Article
- Enhancing dopaminergic signaling and histone acetylation promotes long-term rescue of deficient fear extinction.Translational psychiatry · 2016Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundDespite its success in treating specific anxiety disorders, the effect of exposure therapy is limited by problems with tolerability, treatment resistance, and fear relapse after initial response. The identification of novel drug targets facilitating fear extinction in clinically relevant animal models may guide improved treatment strategies for these disorders in terms of efficacy, acceleration of fear extinction, and return of fear.
methodsThe extinction-facilitating potential of neuropeptide S, D-cycloserine, and a benzodiazepine was investigated in extinction-impaired high anxiety HAB rats and 129S1/SvImJ mice using a classical cued fear conditioning paradigm followed by extinction training and several extinction test sessions to study fear relapse.
resultsAdministration of D-cycloserine improved fear extinction in extinction-limited, but not in extinction-deficient, rodents compared with controls. Preextinction neuropeptide S caused attenuated fear responses in extinction-deficient 129S1/SvImJ mice at extinction training onset and further reduced freezing during this session. While the positive effects of either D-cycloserine or neuropeptide S were not persistent in 129S1/SvImJ mice after 10 days, the combination of preextinction neuropeptide S with postextinction D-cycloserine rendered the extinction memory persistent and context independent up to 5 weeks after extinction training. This dual pharmacological adjunct to extinction learning also protected against fear reinstatement in 129S1/SvImJ mice.
conclusionsBy using the potentially nonsedative anxiolytic neuropeptide S and the cognitive enhancer D-cycloserine to facilitate deficient fear extinction, we provide here the first evidence of a purported efficacy of a dual over a single drug approach. This approach may render exposure sessions less aversive and more efficacious for patients, leading to enhanced protection from fear relapse in the long term.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.