ArticleThe international journal of neuropsychopharmacology2015
Increased Contextual Fear Conditioning in iNOS Knockout Mice: Additional Evidence for the Involvement of Nitric Oxide in Stress-Related Disorders and Contribution of the Endocannabinoid System.
Article in The international journal of neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 58 citations in OpenAlex.
- Radical Revelations: The Interplay of Nitrosative Stress, the Endocannabinoid System, and Treatment of Age-Related Disorders.International journal of molecular sciences · 2026Review
- Rosiglitazone Adjunct to Risperidone for Irritability in Autistic Children: A Randomized, Double-Blind, Placebo-Controlled Trial.Journal of autism and developmental disorders · 2025Article
- "NO" Time in Fear Response: Possible Implication of Nitric-Oxide-Related Mechanisms in PTSD.Molecules (Basel, Switzerland) · 2023Review
- Endocannabinoid signaling and epigenetics modifications in the neurobiology of stress-related disorders.Neuronal signaling · 2023Review
- Inflammation and Nitro-oxidative Stress as Drivers of Endocannabinoid System Aberrations in Mood Disorders and Schizophrenia.Molecular neurobiology · 2022Review
- Inducible Nitric Oxide Synthase Inhibition in the Medial Prefrontal Cortex Attenuates the Anxiogenic-Like Effect of Acute Restraint StressFrontiers in psychiatry · 2022Article
- The 4-(Phenylsulfanyl) butan-2-one Improves Impaired Fear Memory Retrieval and Reduces Excessive Inflammatory Response in Triple Transgenic Alzheimer's Disease Mice.Frontiers in aging neuroscience · 2021Article
- Genetic Ablation of the Inducible Form of Nitric Oxide in Male Mice Disrupts Immature Neuron Survival in the Adult Dentate Gyrus.Frontiers in immunology · 2021Article
- Downregulation of the CB1-Mediated Endocannabinoid Signaling Underlies D-Galactose-Induced Memory Impairment.Frontiers in molecular neuroscience · 2020Article
- Tempering aversive/traumatic memories with cannabinoids: a review of evidence from animal and human studies.Psychopharmacology · 2019Review
- Repeated social defeat-induced neuroinflammation, anxiety-like behavior and resistance to fear extinction were attenuated by the cannabinoid receptor agonist WIN55,212-2.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Article
- Salivary Nitric Oxide, a Biomarker for Stress and Anxiety?Psychiatry investigation · 2016Article
- Inducible Nitric Oxide Inhibitors Block NMDA Antagonist-Stimulated Motoric Behaviors and Medial Prefrontal Cortical Glutamate Efflux.Frontiers in pharmacology · 2015Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInducible or neuronal nitric oxide synthase gene deletion increases or decreases anxiety-like behavior in mice, respectively. Since nitric oxide and endocannabinoids interact to modulate defensive behavior, the former effect could involve a compensatory increase in basal brain nitric oxide synthase activity and/or changes in the endocannabinoid system. Thus, we investigated the expression and extinction of contextual fear conditioning of inducible nitric oxide knockout mice and possible involvement of endocannabinoids in these responses.
methodsWe evaluated the effects of a preferential neuronal nitric oxide synthase inhibitor, 7-nitroindazol, nitric oxide synthase activity, and mRNA changes of nitrergic and endocannabinoid systems components in the medial prefrontal cortex and hippocampus of wild-type and knockout mice. The effects of URB597, an inhibitor of the fatty acid amide hydrolase enzyme, which metabolizes the endocannabinoid anandamide, WIN55,212-2, a nonselective cannabinoid agonist, and AM281, a selective CB1 antagonist, on contextual fear conditioning were also evaluated.
resultsContextual fear conditioning expression was similar in wild-type and knockout mice, but the latter presented extinction deficits and increased basal nitric oxide synthase activity in the medial prefrontal cortex. 7-Nitroindazol decreased fear expression and facilitated extinction in wild-type and knockout mice. URB597 decreased fear expression in wild-type and facilitated extinction in knockout mice, whereas WIN55,212-2 and AM281 increased it in wild-type mice. Nonconditioned knockout mice showed changes in the mRNA expression of nitrergic and endocannabinoid system components in the medial prefrontal cortex and hippocampus that were modified by fear conditioning.
conclusionThese data reinforce the involvement of the nitric oxide and endocannabinoids (anandamide) in stress-related disorders and point to a deregulation of the endocannabinoid system in situations where nitric oxide signaling is increased.
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