The fatty acid amide hydrolase inhibitor URB597 modulates splenic catecholamines in chronically stressed female and male rats

Autor: Harisa Ferizovic, Milica M. Jankovic, Bojana Stefanovic, Natasa Spasojevic, Sladjana Dronjak
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Anxiety
chemistry.chemical_compound
Catecholamines
0302 clinical medicine
Fatty acid amide hydrolase
Immunology and Allergy
Interleukin
Endocannabinoid system
Interleukin-10
3. Good health
Neuroprotective Agents
medicine.anatomical_structure
Lymphatic system
030220 oncology & carcinogenesis
Benzamides
Female
medicine.drug
medicine.medical_specialty
Immunology
Spleen
Catechol O-Methyltransferase
Stress
Amidohydrolases
03 medical and health sciences
Sex Factors
Immune system
Stress
Physiological
Internal medicine
medicine
Animals
Rats
Wistar
Monoamine Oxidase
Pharmacology
Interleukin-6
Phenylethanolamine N-Methyltransferase
URB597
030104 developmental biology
Endocrinology
Anti-Anxiety Agents
chemistry
Catecholamine
Carbamates
Catecholamine Plasma Membrane Transport Proteins
Open Field Test
Endocannabinoids
Zdroj: International Immunopharmacology
ISSN: 1567-5769
DOI: 10.1016/j.intimp.2020.106615
Popis: The changes in sympathetic innervations in lymphoid organs could be a key factor in immune dysregulation. The endocannabinoid system has been shown to exhibit potent immunomodulatory effects that may differ between males and females, representing a potential therapeutic target for peripheral and central inflammatory disorders. Thus, in the present study, an examination was made of the effect of fatty acid amide hydrolase inhibitor URB597 treatment on splenic catecholamine content, synthesis, uptake and degradation in chronically unpredictably stressed (CUS) female and male rats. The results show that CUS increases anxiety-like behaviors and that URB597 had an anxiolytic effect on chronically stressed animals of both sexes. CUS induced the expression of plasma interleukin - 6 (IL-6), interleukin - 10 (IL-10) and IL-6 in the spleen, whereas the expression of IL-10 was reduced in the spleen of both sexes. URB597 treatment did not cause changes in IL-6 in plasma or the spleen, whereas it increased IL-10 in the spleen in CUS animals of both sexes. CUS caused a significant depletion of noradrenaline content in the spleen of female rats and a reduction in noradrenaline uptake in the spleen of female rats, while stressed males had a small but insignificant decrease of splenic noradrenaline levels and an enhanced uptake. The FAAH inhibitor URB597 enhances reduced noradrenaline content, affecting its uptake directly at the level of the spleen. It gives rise to the possibility that endocannabinoids exert a neurorestorative effect on the sympathetic nerve system and cell-mediated immune responses in the spleen of chronically stressed rats.
Databáze: OpenAIRE
Externí odkaz: