GeneSet Information

Tier IV GS409096 • Target immune protein expression change in rat hippocampus (HIP) during short-term abstinence following high fentanyl intake compared to saline control_FC

DESCRIPTION:

Male, Sprague-Dawley rats (n = 17); Envigo, Indianapolis, IN) weighing between 250 and 300 g at the start of experiments were used. Rats were trained to lever press for fentanyl (0.0032 mg/kg/0.1 mL infusion) or saline (0.1 mL/inf) using established methods (Neelakantan et al., 2017). Two rats were excluded due to loss of catheter patency. Twenty-four hours following the final self-administration session, rats were sacrificed for molecular biology analyses (n = 15). Due to individual differences and variability in the levels of opioid intake, animals sacrificed for molecular analyses were stratified according to lifetime fentanyl intake: 0 mg/kg fentanyl [i.e., saline self-administration rats (n = 5)], <1.2 mg/kg fentanyl [“low” self-administration rats (n = 5)] and >1.2 mg/kg fentanyl [“high” self-administration rats (n = 5)]. Protein homogenates from the NAc, CPu, and HIP were assayed by a BioPlex immunoassay panel that includes granulocyte–macrophage colony stimulating factor (GMCSF), granulocyte-colony stimulating factor (GCSF), interferon gamma (IFNγ), IL1 β, monocyte chemoattractant protein 1 (MCP1), interleukin (IL)2, IL4, IL5, IL7, IL10, IL12 active heterodimer (IL12p70), IL17A, IL18, macrophage inflammatory protein 3 (MIP3 α), chemokine ligand 5 (RANTES) and tumor necrosis factor alpha (TNF α) (see Heat Map).

LABEL:

Immune protein expression change in rat HIP after high fentanyl intake abstinence vs. control_FC

SCORE TYPE:

Effect

THRESHOLD:

<= 0.5

GENES IN THRESHOLD:

0

DATE ADDED:

2024-09-30

DATE UPDATED:

2025-06-23

SPECIES:

AUTHORS:

Chiomah Ezeomah, Kathryn A Cunningham, Sonja J Stutz, Robert G Fox, Natalya Bukreyeva, Kelly T Dineley, Slobodan Paessler, Irma E Cisneros

TITLE:

Fentanyl self-administration impacts brain immune responses in male Sprague-Dawley rats.

JOURNAL:

Brain, behavior, and immunity 07 2020, Vol 87, pp. 725-738

ABSTRACT:

Opioid use disorder (OUD) affects over two million in the United States and is an increasing public health crisis. The abuse of fentanyl and the emergence of potent fentanyl derivatives increases the risk for the user to succumb to overdose, but also to develop OUD. While intense attention is currently focused on understanding the complexity of behaviors and neural functions that contribute to OUD, much remains to be discovered concerning the interactions of opioid intake with the immune response in the central nervous system (CNS). In the present studies, we tested the hypothesis that short-term abstinence from fentanyl self-administration associates with altered expression of innate immune markers. Male Sprague-Dawley rats were trained to self-administer fentanyl (0.0032 mg/kg/infusion) to stability followed by 24 h of abstinence. Several innate immune markers, as well as opioid receptors (ORs) and intracellular pattern recognition receptors (PRRs), were interrogated within nodes of the neurocircuitry involved in OUD processes, including the prefrontal cortex (PFC), nucleus accumbens (NAc), caudate putamen (CPu), hippocampus (HIP) and midbrain (MB). In the present study, few immune targets were impacted in the PFC and MB during short-term abstinence from fentanyl (relative to saline) self-administration. However, increased expression of cytokines [e.g., interleukin (IL)1β, IL5], chemokines [e.g., C-C motif chemokine 20 (MIP3α)], tumor necrosis factor α (TNFα) and interferon (IFN) proteins (e.g., IFNβ and IFNγ)] was seen in the NAc, while decreased expression of cytokines (e.g., several ILs), chemokines [e.g., granulocyte-macrophage colony-stimulating factor (GMCSF), monocyte chemoattractant protein (MCP) MCP1, MIP3α], the chemokine ligand 5 (RANTES) and interferons (e.g., IFNβ and IFNγ) in the HIP. Positive correlations were observed between cumulative fentanyl intake and expression of IL1β and IL6 in the NAc, and significant negative correlations with fentanyl intake and IFN β, IL2, IL5, IL12p70 and IL17 in the HIP. Few changes in OR expression was observed during early abstinence from fentanyl self-administration. Excitingly, the expression of the PRR, stimulator of interferon genes (STING) negatively correlated with cumulative fentanyl intake and significantly correlated to specific cytokines, chemokines and interferon proteins in the HIP. Although the CPu appears relatively invulnerable to changes in innate immune markers, the highest correlations between cumulative fentanyl intake with MAVS and/or STING was measured in the CPu. Our findings provide the first evidence of CNS innate immune responses and implicate STING as novel mechanistic targets of immunomodulation during short-term abstinence from fentanyl self-administration. PUBMED: 32165150
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Annotation Information

No sequence read archive data associated with this GeneSet.


Granulocytes (D006098)
Macrophage Inflammatory Proteins (D019402)
Chemotactic Factors (D002630)
Tumor Necrosis Factor-alpha (D014409)
Chemokine CCL5 (D018946)
Monocyte Chemoattractant Proteins (D018945)
Mesencephalon (D008636)
Cytokines (D016207)
Behavior (D001519)
Fentanyl (D005283)
Putamen (D011699)
Ligands (D008024)
Immunity (D007109)
Biological Markers (D015415)
Interleukin-12 (D018664)
Opioid-Related Disorders (D009293)
Neoplasms (D009369)
Central Nervous System (D002490)
Public Health (D011634)
Attention (D001288)
Interleukin-10 (D016753)
Proteins (D011506)
Porcine Reproductive and Respiratory Syndrome (D019318)
Risk (D012306)
Immunomodulation (D056747)
Chemokine CCL2 (D018932)
Monocytes (D009000)
Prefrontal Cortex (D017397)
Molecular Biology (D008967)
Nervous System (D009420)
Rats (D051381)
Nucleus Accumbens (D009714)
Interleukin-6 (D015850)
Interleukin-7 (D015851)
Colony-Stimulating Factors (D003115)
Interleukin-2 (D007376)
Interferons (D007372)
Interleukins (D007378)
Affect (D000339)
Immunity, Innate (D007113)
Immunoassay (D007118)
Chemokines (D018925)
Macrophages (D008264)
Interleukin-18 (D020382)
Receptors, Pattern Recognition (D051192)
Receptors, Opioid (D011957)
Catheters (D057785)
Necrosis (D009336)
Interleukin-4 (D015847)
Interleukin-5 (D015848)
Analgesics, Opioid (D000701)
Rats, Sprague-Dawley (D017207)
Hippocampus (D006624)
caudate-putamen (MA:0000893)
accumbens nucleus (MA:0000892)
putamen (MA:0000895)
frontal association cortex (MA:0000906)
midbrain (MA:0000207)
central nervous system (MA:0000167)
nervous system (MA:0000016)
hippocampus (MA:0000191)
cell killing (GO:0001906)
cell death (GO:0008219)
necrotic cell death (GO:0070265)
intracellular (GO:0005622)
threonine-type endopeptidase activity (GO:0004298)
nascent polypeptide-associated complex (GO:0005854)
polyhedral organelle (GO:0031469)
immune response (GO:0006955)
binding (GO:0005488)
cytolysis (GO:0019835)
tumor necrosis factor receptor binding (GO:0005164)
Heat map (EDAM_data:1636)
Prediction, detection and recognition (EDAM_operation:2423)
Genetics (EDAM_topic:3053)
protein (EDAM_format:1208)
Transcriptomics (EDAM_topic:0203)
Small molecules (EDAM_topic:0154)
Pathways, networks and models (EDAM_topic:0602)
Protein analysis (EDAM_topic:0078)
N-acetyl-L-cysteine (CHEBI:28939)
fentanyl (CHEBI:119915)
protein (CHEBI:36080)
maleate(2-) (CHEBI:30780)
1-methylcyclopropene (CHEBI:132592)
medroxyprogesterone acetate (CHEBI:6716)
NAC (CHEBI:7421)
protein polypeptide chain (CHEBI:16541)
ligand (CHEBI:52214)
(4-chloro-2-methylphenoxy)acetic acid (CHEBI:50099)
perfluorinated compound (CHEBI:134091)
photon (CHEBI:30212)
Sprague Dawley (EFO:0001352)
disease (EFO:0000408)
CCL5 measurement (EFO:0005117)
interleukin (EFO:0004100)
interferon gamma (EFO:0003024)
mean arterial pressure (EFO:0006340)
milligram per kilogram (EFO:0002902)
obsolete_central nervous system (EFO:0000908)
obsolete_accumbens nucleus (EFO:0000906)
saline (EFO:0002677)
immunoassay (MMO:0000098)
putamen (UBERON:0001874)
cortex (UBERON:0001851)
intralingual sulcus (UBERON:0002905)
archicortex (UBERON:0002961)
prefrontal bone (UBERON:0010750)
midbrain (UBERON:0001891)
Ammon's horn (UBERON:0001954)
central nervous system (UBERON:0001017)
nervous system (UBERON:0001016)
hippocampal formation (UBERON:0002421)
male organism (UBERON:0003101)
neural nucleus (UBERON:0000125)
anatomical system (UBERON:0000467)
prefrontal cortex (UBERON:0000451)
hair outer root sheath (UBERON:0005942)
nucleus accumbens (UBERON:0001882)
caudate-putamen (UBERON:0005383)
anatomical projection (UBERON:0004529)
striatum (UBERON:0002435)
pattern recognition receptor activity (GO:0038187)

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Supported by NIH R01 AA18776 jointly funded by NIAAA and NIDA, and JAX Center for Precision Genetics NIH U54 OD 020351

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