ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015
Interaction between the cholecystokinin and endogenous cannabinoid systems in cued fear expression and extinction retention.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- Morphological and electrophysiological diversity and connectivity of principal neurons in the lateral and basal nuclei of the mouse amygdala.Scientific reports · 2025Article
- Cannabinoid overrides triggers of GABAergic plasticity in vestibular circuits and distorts the development of navigation.iScience · 2025Article
- Spatial Cell Atlas of Lateral Septum Reveals Changes Underlying Anxiety and Fear Learning Deficits in Mice with Abnormal Immunity.International journal of biological sciences · 2025Article
- Divergent input patterns to the central lateral amygdala play a duet in fear memory formation.iScience · 2024Article
- Herbal Cannabis and Depression: A Review of Findings Published over the Last Three Years.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Biomarkers of stress resilience: A review.Neuroscience applied · 2024Article
- Anxiety Modulation by Cannabinoids-The Role of Stress Responses and Coping.International journal of molecular sciences · 2023Review
- Expression of the type 1 cannabinoid receptor (CB1R) in CCK-immunoreactive axon terminals in the basolateral amygdala of the rhesus monkey (Macaca mulatta).Neuroscience letters · 2021Article
- Cholecystokinin-Mediated Neuromodulation of Anxiety and Schizophrenia: A "Dimmer-Switch" Hypothesis.Current neuropharmacology · 2021Review
- Gene Transcript Alterations in the Spinal Cord, Anterior Cingulate Cortex, and Amygdala in Mice Following Peripheral Nerve Injury.Frontiers in cell and developmental biology · 2021Article
- Functional neuroanatomy of the basolateral amygdala: Neurons, neurotransmitters, and circuits.Handbook of behavioral neuroscience · 2020Article
- Endocannabinoid System Components as Potential Biomarkers in Psychiatry.Frontiers in psychiatry · 2020Review
- Cholecystokinin immunoreactive neurons in the basolateral amygdala of the rhesus monkey (Macaca mulatta).The Journal of comparative neurology · 2019Article
- Sex differences in fear extinction.Neuroscience and biobehavioral reviews · 2019Review
- Cannabinoid CBNature medicine · 2019Article
- Acute and long-lasting effects of oxytocin in cortico-limbic circuits: consequences for fear recall and extinction.Psychopharmacology · 2019Review
- Enhancing Endocannabinoid Neurotransmission Augments The Efficacy of Extinction Training and Ameliorates Traumatic Stress-Induced Behavioral Alterations in Rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Elucidating the mechanisms of fear extinction in developing animals: a special case of NMDA receptor-independent extinction in adolescent rats.Learning & memory (Cold Spring Harbor, N.Y.) · 2018Article
- Integrating Endocannabinoid Signaling and Cannabinoids into the Biology and Treatment of Posttraumatic Stress Disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Review
- Effects of vagus nerve stimulation on extinction of conditioned fear and post-traumatic stress disorder symptoms in rats.Translational psychiatry · 2017Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Post-traumatic stress disorder (PTSD) is thought to develop, in part, from improper inhibition of fear. Accordingly, one of the most effective treatment strategies for PTSD is exposure-based psychotherapy. Ideally, neuroscience would inform adjunct therapies that target the neurotransmitter systems involved in extinction processes. Separate studies have implicated the cholecystokinin (CCK) and endocannabinoid systems in fear; however, there is a high degree of anatomical colocalization between the cannabinoid 1 receptor (Cnr1) and CCK in the basolateral amygdala (BLA), a brain region critical for emotion regulation. Although most research has focused on GABA and GABAergic plasticity as the mechanism by which Cnr1 mediates fear inhibition, we hypothesize that a functional interaction between Cnr1 and CCKB receptor (CCKBR) is critical for fear extinction processes. In this study, systemic pharmacological manipulation of the cannabinoid system modulated cued fear expression in C57BL/6J mice after consolidation of auditory fear conditioning. Knockout of the CCKBR, however, had no effect on fear- or anxiety-like behaviors. Nonetheless, administration of a Cnr1 antagonist increased freezing behavior during a cued fear expression test in wild-type subjects, but had no effect on freezing behavior in CCKBR knockout littermates. In addition, we found that Cnr1-positive fibers form perisomatic clusters around CCKBR-positive cell bodies in the BLA. These CCKBR-positive cells comprise a molecularly heterogenous population of excitatory and inhibitory neurons. These findings provide novel evidence that Cnr1 contributes to cued fear expression via an interaction with the CCK system. Dysfunctional Cnr1-CCKBR interactions might contribute to the etiology of, or result from, fear-related psychiatric disease.
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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.