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Endocannabinoid signaling dissociates thermoregulatory and behavioral components of the sickness response to systemic inflammation.

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Τίτλος: Endocannabinoid signaling dissociates thermoregulatory and behavioral components of the sickness response to systemic inflammation.
Συγγραφείς: Oliveira MK; Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, Universidade Federal de Alfenas (Unifal-MG), Alfenas, MG, Brazil., Vilela FC; Centro de Inovação e Ensaios Pré-Clinicos (CIEnP), Florianópolis, SC, Brazil., Giusti-Paiva A; Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas, Universidade Federal de Alfenas (Unifal-MG), Alfenas, MG, Brazil; Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil. Electronic address: agiustipaiva@gmail.com.
Πηγή: Behavioural brain research [Behav Brain Res] 2026 Oct 18; Vol. 515, pp. 116447. Date of Electronic Publication: 2026 Aug 21.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 8004872 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7549 (Electronic) Linking ISSN: 01664328 NLM ISO Abbreviation: Behav Brain Res Subsets: MEDLINE
Imprint Name(s): Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press.
Ιατρικοί όροι (MeSH): Endocannabinoids*/metabolism , Illness Behavior*/physiology , Illness Behavior*/drug effects , Body Temperature Regulation*/drug effects , Body Temperature Regulation*/physiology , Inflammation*/metabolism , Inflammation*/chemically induced , Inflammation*/physiopathology , Receptor, Cannabinoid, CB1*/antagonists & inhibitors , Receptor, Cannabinoid, CB1*/metabolism , Receptor, Cannabinoid, CB1*/agonists , Behavior, Animal*/drug effects , Behavior, Animal*/physiology, Lipopolysaccharides/pharmacology ; Naphthalenes/pharmacology ; Pyrazoles/pharmacology ; Piperidines/pharmacology ; Morpholines/pharmacology ; Benzoxazines/pharmacology ; Signal Transduction/drug effects ; Body Temperature/drug effects ; Eating/drug effects ; Animals ; Male ; Rats, Wistar ; Rats ; Fever
Περίληψη: Systemic inflammation triggers a coordinated sickness response that includes behavioral suppression, anorexia, and thermoregulatory alterations, often viewed as a unified syndrome. However, increasing evidence suggests that distinct neural circuits govern different components of sickness behavior. Whether central endocannabinoid system (ECS) signaling differentially regulates behavioral and thermoregulatory responses during systemic inflammation remains unclear. We therefore investigated the role of central ECS signaling in specific sickness domains induced by lipopolysaccharide (LPS). Male Wistar rats received intracerebroventricular pretreatment with the CB1 receptor antagonist AM251, the endocannabinoid transport inhibitor VDM11, the CB1 agonist WIN55,212-2, or vehicle prior to intraperitoneal administration of LPS (1 mg/kg) or saline. Behavioral responses were assessed using the open field test, forced-swim test, and 24-h food intake. Core body temperature was continuously monitored by telemetry for 6 h, and thermal indices were calculated for hypothermia (0-2 h) and fever (3-6 h). LPS induced a robust sickness phenotype characterized by reduced locomotion, increased immobility, hypophagia, and a biphasic thermoregulatory response. Central ECS manipulations produced minimal effects on behavioral endpoints. In contrast, thermoregulation was selectively sensitive to ECS modulation: CB1 receptor blockade enhanced LPS-induced hypothermia and markedly reduced fever, whereas increasing endocannabinoid tone attenuated hypothermia without affecting fever. These findings demonstrate that central ECS signaling selectively modulates thermoregulatory, but not behavioral, components of the sickness response, supporting a modular organization of sickness behavior.
(Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved.)
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: CB1 receptor; Fever; Hypothermia; Lipopolysaccharide; Neuroimmune interaction; Thermoregulation
Substance Nomenclature: 0 (Lipopolysaccharides)
0 (Endocannabinoids)
0 (Receptor, Cannabinoid, CB1)
0 (Naphthalenes)
0 (Pyrazoles)
0 (Piperidines)
0 (Morpholines)
0 (Benzoxazines)
3I4FA44MAI (AM 251)
5H31GI9502 ((3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone)
Entry Date(s): Date Created: 20260821 Date Completed: 20260904 Latest Revision: 20260904
Update Code: 20260905
DOI: 10.1016/j.bbr.2026.116447
PMID: 42628845
Βάση Δεδομένων: MEDLINE
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  Data: Endocannabinoid signaling dissociates thermoregulatory and behavioral components of the sickness response to systemic inflammation.
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– Name: Abstract
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  Data: Systemic inflammation triggers a coordinated sickness response that includes behavioral suppression, anorexia, and thermoregulatory alterations, often viewed as a unified syndrome. However, increasing evidence suggests that distinct neural circuits govern different components of sickness behavior. Whether central endocannabinoid system (ECS) signaling differentially regulates behavioral and thermoregulatory responses during systemic inflammation remains unclear. We therefore investigated the role of central ECS signaling in specific sickness domains induced by lipopolysaccharide (LPS). Male Wistar rats received intracerebroventricular pretreatment with the CB1 receptor antagonist AM251, the endocannabinoid transport inhibitor VDM11, the CB1 agonist WIN55,212-2, or vehicle prior to intraperitoneal administration of LPS (1 mg/kg) or saline. Behavioral responses were assessed using the open field test, forced-swim test, and 24-h food intake. Core body temperature was continuously monitored by telemetry for 6 h, and thermal indices were calculated for hypothermia (0-2 h) and fever (3-6 h). LPS induced a robust sickness phenotype characterized by reduced locomotion, increased immobility, hypophagia, and a biphasic thermoregulatory response. Central ECS manipulations produced minimal effects on behavioral endpoints. In contrast, thermoregulation was selectively sensitive to ECS modulation: CB1 receptor blockade enhanced LPS-induced hypothermia and markedly reduced fever, whereas increasing endocannabinoid tone attenuated hypothermia without affecting fever. These findings demonstrate that central ECS signaling selectively modulates thermoregulatory, but not behavioral, components of the sickness response, supporting a modular organization of sickness behavior.<br /> (Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved.)
– Name: Abstract
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  Data: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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  Data: <i>Keywords: </i>CB1 receptor; Fever; Hypothermia; Lipopolysaccharide; Neuroimmune interaction; Thermoregulation
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        Text: English
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