Effects of early life stress on cocaine conditioning and AMPA receptor composition are sex-specific and driven by TNF
Autor: | Jennifer A. Honeycutt, Heather C. Brenhouse, June R. Rowe, Prabarna Ganguly, Camila Demaestri |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male medicine.medical_specialty medicine.medical_treatment Immunology Conditioning Classical Prefrontal Cortex Ibudilast AMPA receptor Nucleus accumbens Nucleus Accumbens Article Rats Sprague-Dawley 03 medical and health sciences Behavioral Neuroscience 0302 clinical medicine Sex Factors Cocaine Internal medicine medicine Animals Receptors AMPA Phosphodiesterase inhibitor Endocrine and Autonomic Systems business.industry Tumor Necrosis Factor-alpha Maternal Deprivation Glutamate receptor Brain Conditioned place preference Rats 030104 developmental biology Cytokine Endocrinology nervous system Conditioning Operant Tumor necrosis factor alpha Female business 030217 neurology & neurosurgery Stress Psychological medicine.drug |
Zdroj: | Brain Behav Immun |
ISSN: | 1090-2139 |
Popis: | Exposure to early life adversity can predispose adolescents to the formation of substance abuse disorders. In rodents, early stressors such as repeated maternal separation (MS) impact AMPAR activity in the prefrontal cortex (PFC) and nucleus accumbens (NAc), regions involved in drug-cue association after cocaine-induced conditioned place preference (CPP). Notably, previous reports suggest that the pro-inflammatory cytokine tumor necrosis factor (TNF) regulates AMPAR subunit composition; increased TNF levels are reported to reduce GluA2-positive AMPARs. Since MS can elevate adolescent TNF levels, the stressor may therefore alter AMPAR subunit composition via neuroimmune signaling, thereby affecting cocaine-induced CPP. We tested the specific role of soluble TNF in MS-induced GluA2 loss and cocaine-induced CPP with biologic disruption of TNF signaling. TNF gene and protein expression were elevated in both PFC and NAc of MS males, but not females. GluA2 expression was reduced in both regions in only male MS rats, and systemic treatment with either ibudilast – a phosphodiesterase inhibitor, or XPro1595 – a blood-brain barrier-permeable blocker of soluble TNF – reversed such loss. MS males also formed greater preference for a cocaine-paired environment, the expression of which returned to control levels after XPro1595 administration. These data suggest a sex-specific mechanistic link between TNF signaling and changes in GluA2 expression and drug-cue conditioning, thereby providing further evidence for a role of MS and neuro-immune activity in cortical and striatal AMPAR changes. Moreover, manipulation of the TNF signaling pathway represents a novel approach for influencing response to reinforcing effects of drug use. |
Databáze: | OpenAIRE |
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