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Neuroimmune Signaling in The Regulation of Cocaine- and Opioid-Seeking Behaviors
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Neuroimmune Signaling in The Regulation of Cocaine- and Opioid-Seeking Behaviors. |
| 개인저자 | Brown, Kyle T. |
| 단체저자명 | University of Colorado at Boulder. Psychology. |
| 발행사항 | [S.l.]: University of Colorado at Boulder., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 145 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-04B. Dissertation Abstract International |
| ISBN | 9781088301159 |
| 학위논문주기 | Thesis (Ph.D.)--University of Colorado at Boulder, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Advisor: Bachtell, Ryan. |
| 이용제한사항 | This item must not be sold to any third party vendors.This item must not be added to any third party search indexes. |
| 요약 | The abuse of cocaine and opioids is a major public health threat, yet, to date, therapies aimed at treating these disorders have limited efficacy. Preventing relapse is a major goal in the treatment of individuals that meet the criteria for a substance use disorder. Much research has been directed at understanding neuroadaptations that underlie the uncontrollable bouts of craving that often precipitate relapse. However, a dearth of studies has investigated the potential role of neuroimmune signaling in relapse. Toll-like receptor 4 (TLR4) is a pattern recognition receptor expressed on immune cells that has been indicated in ligating cocaine and opioids and initiating signal transduction of inflammatory cytokine pathways. Recognition of these drugs by TLR4 results in the induction of an innate immune response within the mesolimbic dopamine system. In turn, this mesolimbic dopamine response has been indicated to alter dopamine signaling and contribute to the reinforcing effects of drugs of abuse. However, it is unknown whether TLR4 effects may extend to drug-seeking behavior characteristic of drug-relapse. To investigate this question, the studies outlined here employ rodent self-administration models of cocaine and opioid relapse-like behavior to investigate the potential role of neuroimmune signaling. TLR4 antagonists applied into the VTA and NAc Shell, but not NAc Core, were found to reduce cocaine-seeking behavior. Conversely, the TLR4 agonist LPS administered into the VTA moderately induced drug-seeking. Manipulating pro-inflammatory and anti-inflammatory signaling in the NAc Core had no clear interpretable effect on incubation of cocaine craving. Oxycodone self-administration was reduced in the incubation of craving model following systemic administration of the glia inhibitor Ibudilast throughout the course of withdrawal. Reduction in incubation of oxycodone drug-seeking of the Ibudilast group was accompanied by a decrease in expression of the astrocyte gliosis marker GFAP. However, Ibudilast also reduced self-administration of sucrose, complicating the interpretation of specificity of Ibudilast's behavioral effects. Together, these data indicate a role of neuroimmune signaling in drug-seeking behaviors for cocaine and oxycodone. |
| 일반주제명 | Neurosciences. Clinical psychology. Public health. Health sciences. Psychobiology. Behavioral psychology. Physiological psychology. |
| 언어 | 영어 |
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