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Dysregulation of Inflammatory Immune Responses: Effect of Stress Paradigms in a Rat Model of Novelty‐seeking Phenotype
Author(s) -
IragavarapuCharyulu Vijaya L.,
Libreros Stephania,
Garcia Ramon A.,
Isgor Ceylan
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.946.13
Subject(s) - nicotine , craving , immune system , tumor necrosis factor alpha , cytokine , pharmacology , immunology , medicine , endocrinology , addiction , psychiatry
Behavior and stress affect immune responses. A rat model of human sensation‐seeking/risk‐taking trait for drug and stress vulnerability, based on their exploratory behavior displaying h igh r ates (HRs) or l ow r ates of locomotor reactivity (LRs) to environmental stress was used to study the relationship between the neuroimmunologic systems. Exposure to chronic, variable physical stress (CVP) or chronic, variable social stress (CVS) during nicotine training resulted in the HR but not LR phenotype to develop nicotine craving with dysregulated stress axis activation following nicotine exposure. In contrast, CVP with nicotine caused emergence of an HR‐like craving in the LRs, and conversely the CVS with nicotine suppressed the craving normally observed in the HRs. Baseline immune responses differed in LR‐HR rats. These differences were further impacted by exposure to the two types of stress regimen: HR rats’ T‐cells responded to nicotine with increased tumor necrosis factor alpha (TNF‐α) and decreased interferon‐γ (IFN‐γ) production compared to LRs. Immune response impacted by stress is associated with secretion of glucocorticoids (GC) which bind to GC receptors (GRs) with inhibition of inflammatory gene transcription. A potential deficit in the GR‐mediated trans‐repression of inflammatory gene expression via the histone deacetylase 2 (HDAC2) pathways may be involved in the HR‐like vulnerability in the pro‐inflammatory cytokine response to nicotine. This project is supported by: JEK Florida Biomedical Research Grant (05NIR‐06‐5194).