Hippocampal TNF-α Signaling Mediates Heroin Withdrawal-Enhanced Fear Learning and Withdrawal-Induced Weight Loss
| العنوان: | Hippocampal TNF-α Signaling Mediates Heroin Withdrawal-Enhanced Fear Learning and Withdrawal-Induced Weight Loss |
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| المؤلفون: | Donald T. Lysle, Lydia O. Adams, Shveta V. Parekh, Jacqueline E. Paniccia |
| المصدر: | Molecular Neurobiology |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, Neuroscience (miscellaneous), Opioid, Neuroimmune, Hippocampal formation, Hippocampus, Article, Etanercept, Heroin, Rats, Sprague-Dawley, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Internal medicine, Weight Loss, medicine, Animals, Learning, Tumor Necrosis Factor-alpha, business.industry, Dentate gyrus, PTSD, Opioid use disorder, Fear, medicine.disease, Substance Withdrawal Syndrome, 030104 developmental biology, Endocrinology, Neurology, Withdrawal, TNF-α, Cytokines, Anxiety, Tumor necrosis factor alpha, medicine.symptom, business, 030217 neurology & neurosurgery, Signal Transduction, medicine.drug |
| الوصف: | There is significant comorbidity of opioid use disorder (OUD) and post-traumatic stress disorder (PTSD) in clinical populations. However, the neurobiological mechanisms underlying the relationship between chronic opioid use and withdrawal and development of PTSD are poorly understood. Our previous work identified that chronic escalating heroin administration and withdrawal can produce enhanced fear learning, an animal model of hyperarousal, and is associated with an increase in dorsal hippocampal (DH) interleukin-1β (IL-1β). However, other cytokines, such as TNF-α, work synergistically with IL-1β and may have a role in the development of enhanced fear learning. Based on both translational rodent and clinical studies, TNF-α has been implicated in hyperarousal states of PTSD, and has an established role in hippocampal-dependent learning and memory. The first set of experiments tested the hypothesis that chronic heroin administration followed by withdrawal is capable of inducing alterations in DH TNF-α expression. The second set of experiments examined whether DH TNF-α expression is functionally relevant to the development of enhanced fear learning. We identified an increase of TNF-α immunoreactivity and positive cells at 0, 24, and 48 h into withdrawal in the dentate gyrus DH subregion. Interestingly, intra-DH infusions of etanercept (TNF-α inhibitor) 0, 24, and 48 h into heroin withdrawal prevented the development of enhanced fear learning and mitigated withdrawal-induced weight loss. Overall, these findings provide insight into the role of TNF-α in opioid withdrawal and the development of anxiety disorders such as PTSD. |
| تدمد: | 1559-1182 0893-7648 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3b6fa53a2a0248ecbeeab9daf80073c8 https://doi.org/10.1007/s12035-021-02322-z |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3b6fa53a2a0248ecbeeab9daf80073c8 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15591182 08937648 |
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