ArticleMolecular psychiatry2021
The ERK phosphorylation levels in the amygdala predict anxiety symptoms in humans and MEK/ERK inhibition dissociates innate and learned defensive behaviors in rats.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 29 citations in OpenAlex.
- Acute unilateral DBS of the basolateral amygdala does not affect motricity, anxiety-like behavior, or fear memory consolidation in rats.Experimental brain research · 2026Article
- MAPK/ERK pathway is necessary to the reconsolidation of fear memory in male and female rats.Psychopharmacology · 2026Article
- Chronic Hyponatremia Potentiates Innate Anxiety-Like Behaviors Through the Dysfunction of Monoaminergic Neurons in Mice.Molecular neurobiology · 2025Article
- Cross-ancestry and sex-stratified genome-wide association analyses of amygdala and subnucleus volumes.Nature genetics · 2025Article
- Astragalin relieves inflammatory pain and negative mood in CFA mice by down-regulating mGluR5 signaling pathway.Scientific reports · 2025Article
- Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms.Biomedicines · 2024Review
- Inhibition of fatty acid binding protein-5 in the basolateral amygdala induces anxiolytic effects and accelerates fear memory extinction.Psychopharmacology · 2024Article
- Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications.Frontiers in pharmacology · 2024Review
- Carbon dioxide and MAPK signalling: towards therapy for inflammation.Cell communication and signaling : CCS · 2023Review
- Transcriptional Profiling of Rat Prefrontal Cortex after Acute Inescapable Footshock Stress.Genes · 2023Article
- Reversal of hyperactive higher-order thalamus attenuates defensiveness in a mouse model of PTSD.Science advances · 2023Article
- Blood transcriptome analysis suggests an indirect molecular association of early life adversities and adult social anxiety disorder by immune-related signal transduction.Frontiers in psychiatry · 2023Article
- Epigenome-wide DNA methylation analysis of whole blood cells derived from patients with GAD and OCD in the Chinese Han population.Translational psychiatry · 2022Article
- Adolescent fluoxetine exposure increases ERK-related signaling within the prefrontal cortex of adult male Sprague-Dawley rats.Oxford open neuroscience · 2022Article
- Functional Connectivity Features of Resting-State Functional Magnetic Resonance Imaging May Distinguish Migraine From Tension-Type Headache.Frontiers in neuroscience · 2022Article
- Early Life Stress Induces Different Behaviors in Adolescence and Adulthood May Related With Abnormal Medial Prefrontal Cortex Excitation/Inhibition Balance.Frontiers in neuroscience · 2021Article
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14 authors at 4 institutions in 3 countries.
Funding
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Abstract
We demonstrate that the rate of extracellular signal-related kinase phosphorylation (P-ERK1,2/Total-ERK1,2) in the amygdala is negatively and independently associated with anxiety symptoms in 23 consecutive patients with drug-resistant mesial temporal lobe epilepsy that was surgically treated. In naive Wistar rats, the P-ERK1,2/Total-ERK1,2 ratio in the amygdala correlates negatively with innate anxiety-related behavior on the elevated plus maze (n = 20) but positively with expression of defensive-learned behavior (i.e., freezing) on Pavlovian aversive (fear) conditioning (n = 29). The microinfusion of ERK1/2 inhibitor (FR180204, n = 8-13/group) or MEK inhibitor (U0126, n = 8-9/group) into the basolateral amygdala did not affect anxiety-related behavior but impaired the evocation (anticipation) of conditioned-defensive behavior (n = 9-11/group). In conclusion, the P-ERK1,2/Total-ERK1,2 ratio in the amygdala predicts anxiety in humans and the innate anxiety- and conditioned freezing behaviors in rats. However, the ERK1/2 in the basolateral AMY is only required for the expression of defensive-learned behavior. These results support a dissociate ERK-dependent mechanism in the amygdala between innate anxiety-like responses and the anticipation of learned-defensive behavior. These findings have implications for understanding highly prevalent psychiatric disorders related to the defensive circuit manifested by anxiety and fear. HIGHLIGHTS: The P-ERK1,2/Total-ERK1,2 ratio in the amygdala (AMY) correlates negatively with anxiety symptoms in patients with mesial temporal lobe epilepsy. The P-ERK1,2/Total-ERK1,2 in the amygdala correlates negatively with the anxiety-like behavior and positively with freezing-learned behavior in naive rats. ERK1,2 in the basolateral amygdala is required for learned-defensive but not for the anxiety-like behavior expression in rats.
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