ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Bimodal control of fear-coping strategies by CB₁ cannabinoid receptors.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 99 citations in OpenAlex.
- Hypothalamic POMC Neurons Gate the Fear-Feeding Trade-Off.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Genetic Tools in Rodents to Study Cannabinoid Functions.Current topics in behavioral neurosciences · 2026Review
- Circuit mechanisms governing endocannabinoid modulation of affective behaviour and stress adaptation.Nature reviews. Neuroscience · 2025Review
- Stress reactivity is modulated by cannabinoid type-1 receptors in norepinephrine and epinephrine neurons in a context-dependent manner.Neuroscience · 2025Article
- Profiling mouse behavior with computational tools to assess age-dependent differences in associative learning.Cell reports methods · 2025Article
- Characterization of a Fatty Acid Amide Hydrolase (FAAH) in Hirudo Verbana.Neurochemical research · 2024Article
- Olfactory bulb astrocytes link social transmission of stress to cognitive adaptation in male mice.Nature communications · 2024Article
- Predator odor stress reactivity, alcohol drinking and the endocannabinoid system.Neurobiology of stress · 2024Article
- Cannabinoid type 2 receptor inhibition enhances the antidepressant and proneurogenic effects of physical exercise after chronic stress.Translational psychiatry · 2024Article
- Sexually dimorphic effects of monoacylglycerol lipase inhibitor MJN110 on stress-related behaviour and drinking in Marchigian Sardinian alcohol-preferring rats.British journal of pharmacology · 2023Article
- Imaging and Genetic Tools for the Investigation of the Endocannabinoid System in the CNS.International journal of molecular sciences · 2023Review
- Anxiety Modulation by Cannabinoids-The Role of Stress Responses and Coping.International journal of molecular sciences · 2023Review
- Article
- The Endocannabinoid 2-Arachidonoylglycerol Bidirectionally Modulates Acute and Protracted Effects of Predator Odor Exposure.Biological psychiatry · 2022Article
- Footshock-Induced Abstinence from Compulsive Methamphetamine Self-administration in Rat Model Is Accompanied by Increased Hippocampal Expression of Cannabinoid Receptors (CB1 and CB2).Molecular neurobiology · 2022Article
- Cannabinoid CBFrontiers in neuroanatomy · 2022Article
- Microglial Cannabinoid Type 1 Receptor Regulates Brain Inflammation in a Sex-Specific Manner.Cannabis and cannabinoid research · 2021Article
- The role of endocannabinoids in consolidation, retrieval, reconsolidation, and extinction of fear memory.Pharmacological reports : PR · 2021Review
- Increased alcohol self-administration following exposure to the predator odor TMT in active coping female rats.Behavioural brain research · 2021Article
- The endocannabinoid system in the amygdala and modulation of fear.Progress in neuro-psychopharmacology & biological psychiatry · 2021Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
To maximize their chances of survival, animals need to rapidly and efficiently respond to aversive situations. These responses can be classified as active or passive and depend on the specific nature of threats, but also on individual fear coping styles. In this study, we show that the control of excitatory and inhibitory brain neurons by type-1 cannabinoid (CB₁) receptors is a key determinant of fear coping strategies in mice. In classical fear conditioning, a switch between initially predominant passive fear responses (freezing) and active behaviors (escape attempts and risk assessment) develops over time. Constitutive genetic deletion of CB₁ receptors in CB₁⁻/⁻ mice disrupted this pattern by favoring passive responses. This phenotype can be ascribed to endocannabinoid control of excitatory neurons, because it was reproduced in conditional mutant mice lacking CB₁ receptors from cortical glutamatergic neurons. CB₁ receptor deletion from GABAergic brain neurons led to the opposite phenotype, characterized by the predominance of active coping. The CB₁ receptor agonist Δ⁹-tetrahydrocannabinol exerted a biphasic control of fear coping strategies, with lower and higher doses favoring active and passive responses, respectively. Finally, viral re-expression of CB₁ receptors in the amygdala of CB₁⁻/⁻ mice restored the normal switch between the two coping strategies. These data strongly suggest that CB₁ receptor signaling bimodally controls the spontaneous adoption of active or passive coping strategies in individuals. This primary function of the endocannabinoid system in shaping individual behavioral traits should be considered when studying the mechanisms of physiological and pathological fear.
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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.