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020 ▼a 9781088301159
035 ▼a (MiAaPQ)AAI13895820
040 ▼a MiAaPQ ▼c MiAaPQ ▼d 247004
0820 ▼a 152
1001 ▼a Brown, Kyle T.
24510 ▼a Neuroimmune Signaling in The Regulation of Cocaine- and Opioid-Seeking Behaviors.
260 ▼a [S.l.]: ▼b University of Colorado at Boulder., ▼c 2019.
260 1 ▼a Ann Arbor: ▼b ProQuest Dissertations & Theses, ▼c 2019.
300 ▼a 145 p.
500 ▼a Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
500 ▼a Advisor: Bachtell, Ryan.
5021 ▼a Thesis (Ph.D.)--University of Colorado at Boulder, 2019.
506 ▼a This item must not be sold to any third party vendors.
506 ▼a This item must not be added to any third party search indexes.
520 ▼a 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.
590 ▼a School code: 0051.
650 4 ▼a Neurosciences.
650 4 ▼a Clinical psychology.
650 4 ▼a Public health.
650 4 ▼a Health sciences.
650 4 ▼a Psychobiology.
650 4 ▼a Behavioral psychology.
650 4 ▼a Physiological psychology.
690 ▼a 0317
690 ▼a 0573
690 ▼a 0384
690 ▼a 0566
690 ▼a 0349
690 ▼a 0622
690 ▼a 0989
71020 ▼a University of Colorado at Boulder. ▼b Psychology.
7730 ▼t Dissertations Abstracts International ▼g 81-04B.
773 ▼t Dissertation Abstract International
790 ▼a 0051
791 ▼a Ph.D.
792 ▼a 2019
793 ▼a English
85640 ▼u http://www.riss.kr/pdu/ddodLink.do?id=T15491647 ▼n KERIS ▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다.
980 ▼a 202002 ▼f 2020
990 ▼a ***1008102
991 ▼a E-BOOK