Cannabinoid receptor 2 activation mitigates lipopolysaccharide-induced neuroinflammation and sickness behavior in mice

Puspita Sahu, Jayesh Mudgal, Devinder Arora, Manas Kinra, Sanchari Basu Mallik, Chamallamudi Mallikarjuna Rao, K. S.R. Pai, Madhavan Nampoothiri

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Abstract

Rationale and objectives: Cannabinoid receptor 2 (CB2R) signaling in the brain is associated with the pathophysiology of depression. Sickness behavior, characterized by lessened mobility, social interaction, and depressive behavior, is linked with neuroinflammation, oxidative stress, and immune system. The present study was aimed at evaluating 1-phenylisatin (PI), a CB2R agonist, in sickness behavior. Methods: Influence of acute and 7-day activation of CB2R using PI in lipopolysaccharide (LPS)-induced sickness behavior was assessed in mice. An acute injection of LPS (1.5 mg/kg) produced a fully developed sickness behavior in animals within 1 h of administration. The behavioral paradigm was assessed by open field test, forced swim test, and tail suspension test. Further, tumor necrosis factor-α (TNF-α), antioxidant enzymes, and lipid peroxidation were measured in the brain to correlate neuroinflammation and oxidative stress with sickness behavior. Both treatments, PI (20 mg/kg) and imipramine (15 mg/kg), were administered orally (once for acute and once daily for 7-day protocols). Results: LPS elevated the brain TNF-α level, augmented oxidative stress, and induced the sickness behavior in mice. Acute and 7-day treatment of mice with PI significantly reduced the LPS-induced sickness behavior. In addition, PI inhibited the neuroinflammation evidenced by a reduction in brain TNF-α and oxidative stress. Conclusion: Our data propose that acute and long-term activation of CB2R might prevent neuroinflammation and oxidative stress-associated sickness behavior.

Original languageEnglish
Pages (from-to)1829-1838
Number of pages10
JournalPsychopharmacology
Volume236
Issue number6
DOIs
Publication statusPublished - 01-06-2019

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Illness Behavior
Cannabinoid Receptors
Lipopolysaccharides
Oxidative Stress
Tumor Necrosis Factor-alpha
Brain
Hindlimb Suspension
Imipramine
Interpersonal Relations
Lipid Peroxidation
Immune System
Antioxidants
Depression
Injections

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

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title = "Cannabinoid receptor 2 activation mitigates lipopolysaccharide-induced neuroinflammation and sickness behavior in mice",
abstract = "Rationale and objectives: Cannabinoid receptor 2 (CB2R) signaling in the brain is associated with the pathophysiology of depression. Sickness behavior, characterized by lessened mobility, social interaction, and depressive behavior, is linked with neuroinflammation, oxidative stress, and immune system. The present study was aimed at evaluating 1-phenylisatin (PI), a CB2R agonist, in sickness behavior. Methods: Influence of acute and 7-day activation of CB2R using PI in lipopolysaccharide (LPS)-induced sickness behavior was assessed in mice. An acute injection of LPS (1.5 mg/kg) produced a fully developed sickness behavior in animals within 1 h of administration. The behavioral paradigm was assessed by open field test, forced swim test, and tail suspension test. Further, tumor necrosis factor-α (TNF-α), antioxidant enzymes, and lipid peroxidation were measured in the brain to correlate neuroinflammation and oxidative stress with sickness behavior. Both treatments, PI (20 mg/kg) and imipramine (15 mg/kg), were administered orally (once for acute and once daily for 7-day protocols). Results: LPS elevated the brain TNF-α level, augmented oxidative stress, and induced the sickness behavior in mice. Acute and 7-day treatment of mice with PI significantly reduced the LPS-induced sickness behavior. In addition, PI inhibited the neuroinflammation evidenced by a reduction in brain TNF-α and oxidative stress. Conclusion: Our data propose that acute and long-term activation of CB2R might prevent neuroinflammation and oxidative stress-associated sickness behavior.",
author = "Puspita Sahu and Jayesh Mudgal and Devinder Arora and Manas Kinra and Mallik, {Sanchari Basu} and Rao, {Chamallamudi Mallikarjuna} and Pai, {K. S.R.} and Madhavan Nampoothiri",
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Cannabinoid receptor 2 activation mitigates lipopolysaccharide-induced neuroinflammation and sickness behavior in mice. / Sahu, Puspita; Mudgal, Jayesh; Arora, Devinder; Kinra, Manas; Mallik, Sanchari Basu; Rao, Chamallamudi Mallikarjuna; Pai, K. S.R.; Nampoothiri, Madhavan.

In: Psychopharmacology, Vol. 236, No. 6, 01.06.2019, p. 1829-1838.

Research output: Contribution to journalArticle

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AU - Sahu, Puspita

AU - Mudgal, Jayesh

AU - Arora, Devinder

AU - Kinra, Manas

AU - Mallik, Sanchari Basu

AU - Rao, Chamallamudi Mallikarjuna

AU - Pai, K. S.R.

AU - Nampoothiri, Madhavan

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Rationale and objectives: Cannabinoid receptor 2 (CB2R) signaling in the brain is associated with the pathophysiology of depression. Sickness behavior, characterized by lessened mobility, social interaction, and depressive behavior, is linked with neuroinflammation, oxidative stress, and immune system. The present study was aimed at evaluating 1-phenylisatin (PI), a CB2R agonist, in sickness behavior. Methods: Influence of acute and 7-day activation of CB2R using PI in lipopolysaccharide (LPS)-induced sickness behavior was assessed in mice. An acute injection of LPS (1.5 mg/kg) produced a fully developed sickness behavior in animals within 1 h of administration. The behavioral paradigm was assessed by open field test, forced swim test, and tail suspension test. Further, tumor necrosis factor-α (TNF-α), antioxidant enzymes, and lipid peroxidation were measured in the brain to correlate neuroinflammation and oxidative stress with sickness behavior. Both treatments, PI (20 mg/kg) and imipramine (15 mg/kg), were administered orally (once for acute and once daily for 7-day protocols). Results: LPS elevated the brain TNF-α level, augmented oxidative stress, and induced the sickness behavior in mice. Acute and 7-day treatment of mice with PI significantly reduced the LPS-induced sickness behavior. In addition, PI inhibited the neuroinflammation evidenced by a reduction in brain TNF-α and oxidative stress. Conclusion: Our data propose that acute and long-term activation of CB2R might prevent neuroinflammation and oxidative stress-associated sickness behavior.

AB - Rationale and objectives: Cannabinoid receptor 2 (CB2R) signaling in the brain is associated with the pathophysiology of depression. Sickness behavior, characterized by lessened mobility, social interaction, and depressive behavior, is linked with neuroinflammation, oxidative stress, and immune system. The present study was aimed at evaluating 1-phenylisatin (PI), a CB2R agonist, in sickness behavior. Methods: Influence of acute and 7-day activation of CB2R using PI in lipopolysaccharide (LPS)-induced sickness behavior was assessed in mice. An acute injection of LPS (1.5 mg/kg) produced a fully developed sickness behavior in animals within 1 h of administration. The behavioral paradigm was assessed by open field test, forced swim test, and tail suspension test. Further, tumor necrosis factor-α (TNF-α), antioxidant enzymes, and lipid peroxidation were measured in the brain to correlate neuroinflammation and oxidative stress with sickness behavior. Both treatments, PI (20 mg/kg) and imipramine (15 mg/kg), were administered orally (once for acute and once daily for 7-day protocols). Results: LPS elevated the brain TNF-α level, augmented oxidative stress, and induced the sickness behavior in mice. Acute and 7-day treatment of mice with PI significantly reduced the LPS-induced sickness behavior. In addition, PI inhibited the neuroinflammation evidenced by a reduction in brain TNF-α and oxidative stress. Conclusion: Our data propose that acute and long-term activation of CB2R might prevent neuroinflammation and oxidative stress-associated sickness behavior.

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