ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2019
Impaired anandamide/palmitoylethanolamide signaling in hippocampal glutamatergic neurons alters synaptic plasticity, learning, and emotional responses.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence.Frontiers in psychiatry · 2022Pooled it
- Co-ultramicronized palmitoylethanolamide/luteolin normalizes GABAClinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology · 2023Trial
- The Role of Fatty Acid Amide Hydrolase, a Key Regulatory Endocannabinoid Enzyme, in Domain-Specific Cognitive Performance in Psychosis.Schizophrenia bulletin · 2025Article
- Fatty acid amide hydrolase in major depressive episodes: A [Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Fatty-acid amide hydrolase inhibition mitigates Alzheimer's disease progression in mouse models of amyloidosis.The FEBS journal · 2025Article
- A Decades-Long Journey of Palmitoylethanolamide (PEA) for Chronic Neuropathic Pain Management: A Comprehensive Narrative Review.Pain and therapy · 2025Review
- Neonatal supplementation of oleamide during suckling ameliorates maternal postpartum sleep interruption-induced neural impairment and endocannabinoid dysfunction in early adolescent offspring rats.Frontiers in nutrition · 2025Article
- Distinct serum endocannabinoid profiles in treatment-naïve Han Chinese children with ADHD: a case-control pilot study.Frontiers in neurology · 2025Article
- Impacts of hnRNP A1 Splicing Inhibition on the Brain Remyelination Proteome.Journal of neurochemistry · 2025Article
- Alterations of the endocannabinoid system in adolescents with non-suicidal self-injury as a function of childhood maltreatment.Translational psychiatry · 2024Article
- Interactions Between Ferroptosis and Oxidative Stress in Ischemic Stroke.Antioxidants (Basel, Switzerland) · 2024Review
- Inhibition of fatty acid binding protein-5 in the basolateral amygdala induces anxiolytic effects and accelerates fear memory extinction.Psychopharmacology · 2024Article
- Endocannabinoid Hydrolase Inhibitors: Potential Novel Anxiolytic Drugs.Drug design, development and therapy · 2024Review
- Anandamide and 2-arachidonoylglycerol differentially modulate autistic-like traits in a genetic model of autism based on FMR1 deletion in rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- In vivo brain endocannabinoid metabolism is related to hippocampus glutamate and structure - a multimodal imaging study with PET,Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- APPsα Rescues Tau-Induced Synaptic Pathology.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Anandamide Hydrolysis Inhibition Reverses the Long-Term Behavioral and Gene Expression Alterations Induced by MK-801 in Male Rats: Differential CB1 and CB2 Receptor-Mediated Effects.Schizophrenia bulletin · 2022Article
- Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles.Biomedicines · 2022Review
- A common genetic variant in fatty acid amide hydrolase is linked to alterations in fear extinction neural circuitry in a racially diverse, nonclinical sample of adults.Journal of neuroscience research · 2022Article
- Targeting the Endocannabinoid System in the Treatment of Posttraumatic Stress Disorder: A Promising Case of Preclinical-Clinical Translation?Biological psychiatry · 2022Review
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9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endocannabinoid signaling via anandamide (AEA) is implicated in a variety of neuronal functions and considered a promising therapeutic target for numerous emotion-related disorders. The major AEA degrading enzyme is fatty acid amide hydrolase (FAAH). Genetic deletion and pharmacological inhibition of FAAH reduce anxiety and improve emotional responses and memory in rodents and humans. Complementarily, the mechanisms and impact of decreased AEA signaling remain to be delineated in detail. In the present study, using the Cre/loxP system combined with an adeno-associated virus (AAV)-mediated delivery system, FAAH was selectively overexpressed in hippocampal CA1-CA3 glutamatergic neurons of adult mice. This approach led to specific FAAH overexpression at the postsynaptic site of CA1-CA3 neurons, to increased FAAH enzymatic activity, and, in consequence, to decreased hippocampal levels of AEA and palmitoylethanolamide (PEA), but the levels of the second major endocannabinoid 2-arachidonoyl glycerol (2-AG) and of oleoylethanolamide (OEA) were unchanged. Electrophysiological recordings revealed an enhancement of both excitatory and inhibitory synaptic activity and of long-term potentiation (LTP). In contrast, excitatory and inhibitory long-term depression (LTD) and short-term synaptic plasticity, apparent as depolarization-induced suppression of excitation (DSE) and inhibition (DSI), remained unaltered. These changes in hippocampal synaptic activity were associated with an increase in anxiety-like behavior, and a deficit in object recognition memory and in extinction of aversive memory. This study indicates that AEA is not involved in hippocampal short-term plasticity, or eLTD and iLTD, but modulates glutamatergic transmission most likely via presynaptic sites, and that disturbances in this process impair learning and emotional responses.
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Registered trials
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.