Background And Purpose: Endocannabinoid (eCB) signalling gates many aspects of the stress response, including the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis is controlled by corticotropin releasing hormone (CRH) producing neurons in the paraventricular nucleus of the hypothalamus (PVN). Disruption of eCB signalling increases drive to the HPA axis, but the mechanisms subserving this process are poorly understood.
Experimental Approach: Using an array of cellular, endocrine and behavioural readouts associated with activation of CRH neurons in the PVN, we evaluated the contributions of tonic eCB signalling to the generation of a stress response.
Key Results: The CB1 receptor antagonist/inverse agonist AM251, neutral antagonist NESS243 and NAPE PLD inhibitor LEI401 all uniformly increased Fos in the PVN, unmasked stress-linked behaviours, such as grooming, and increased circulating CORT, recapitulating the effects of stress. Similar effects were also seen after direct administration of AM251 into the PVN, while optogenetic inhibition of PVN CRH neurons ameliorated stress-like behavioural changes produced by disruption of eCB signalling.
Conclusions And Implications: These data indicate that under resting conditions, constitutive eCB signalling restricts activation of the HPA axis through local regulation of CRH neurons in the PVN.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/bph.16198 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The Endocannabinoid Activity Remodulation for Psychosis Liability in Youth (EARLY) Study: An Open-Label Feasibility Trial of Ultramicronized-Palmitoylethanolamide Oral Supplementation in Clinical High-Risk State for Psychosis.
Brain Sci
December 2024
Unit of Psychiatry and Eating Disorders, Department of Medicine (DMED), University of Udine, 33100 Udine, Italy.
To date, no psychotropic medication has shown to effectively halt progression to psychosis among individuals at Clinical High-Risk for psychosis (CHR), fueling the search for novel therapeutic agents. Recent evidence supports Palmitoylethanolamide (PEA) signaling as a potential psychosis biomarker, also indicating a therapeutic role for its supplementation in the treatment of psychotic disorders. Nonetheless, the effect of sustained PEA intake in CHR subjects has never been explored so far.
View Article and Find Full Text PDFChemical Probes for Investigating the Endocannabinoid System.
Curr Top Behav Neurosci
January 2025
Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Cannabis sativa has been used therapeutically since early civilizations, with key cannabinoids Δ-tetrahydrocannabinol (THC) 3.1 and cannabidiol characterized in the 1960s, leading to the discovery of cannabinoid receptors type 1 (CBR) and type 2 (CBR) and the endocannabinoid system (ECS) in the 1990s. The ECS, involving endogenous ligands like 2-arachidonoylglycerol (2-AG) 1.
View Article and Find Full Text PDFSynaptic modulation of glutamate in striatum of the YAC128 mouse model of Huntington disease.
Neurobiol Dis
December 2024
Department of Psychiatry, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada. Electronic address:
Background: Altered balance between striatal direct and indirect pathways contributes to early motor, cognitive and psychiatric symptoms in Huntington disease (HD). While degeneration of striatal D2-type dopamine receptor (D2)-expressing indirect pathway medium spiny neurons (iMSNs) occurs prior to that of D1-type dopamine receptor (D1)-expressing direct pathway neurons, altered corticostriatal synaptic function precedes degeneration. D2-mediated signaling on iMSNs reduces their excitability and promotes endocannabinoid (eCB) synthesis, suppressing glutamate release from cortical afferents.
View Article and Find Full Text PDFBrain endocannabinoid control of metabolic and non-metabolic feeding behaviors.
Neurochem Int
December 2024
Basic School of Medicine, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, 260071, China. Electronic address:
The central endocannabinoid (eCB) system in brain shows a crucial role in the regulation of feeding behaviors, influencing both metabolic and non-metabolic mechanisms of appetite control, which has been paid much attention. Although there are already many review articles discussing eCB modulation of feeding behaviors, our paper attempts to summarize the recent advancements through synapses, circuits, and network in brain. Our focus is on the dual role of eCB signalling in regulating metabolic energy balance and hedonic reward-related feeding.
View Article and Find Full Text PDFModulation of the endocannabinoid system by (S)-ketamine in an animal model of depression.
Pharmacol Res
January 2025
Department of Biomedicine, Aarhus University, Denmark; Translational Neuropsychiatry Unit, Aarhus University, Denmark. Electronic address:
Ketamine (KET) is recognized as rapid-acting antidepressant, but its mechanisms of action remain elusive. Considering the role of endocannabinoids (eCB) in stress and depression, we investigated if S-KET antidepressant effects involve the regulation of the eCB system using an established rat model of depression based on selective breeding: the Flinders Sensitive Line (FSL) and their controls, the Flinders Resistant Line (FRL). S-KET (15 mg/kg) effects were assessed in rats exposed to the open field and forced swimming test (FST), followed by analysis of the eCB signaling in the rat prefrontal cortex (PFC), a brain region involved in depression neurobiology.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!