東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

Glutamatergic and Neuroimmune Mechan...

Namba, Mark Douglas.

Linked to FindBook

Google Book

Amazon

博客來

Glutamatergic and Neuroimmune Mechanisms of N-acetylcysteine-mediated Inhibition of Cue-induced Nicotine Seeking.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Glutamatergic and Neuroimmune Mechanisms of N-acetylcysteine-mediated Inhibition of Cue-induced Nicotine Seeking./
Author:	Namba, Mark Douglas.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
Description:	59 p.
Notes:	Source: Masters Abstracts International, Volume: 80-11.
Contained By:	Masters Abstracts International80-11.
Subject:	Neurosciences. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13806032
ISBN:	9781392129869

Glutamatergic and Neuroimmune Mechanisms of N-acetylcysteine-mediated Inhibition of Cue-induced Nicotine Seeking.
Namba, Mark Douglas.

Glutamatergic and Neuroimmune Mechanisms of N-acetylcysteine-mediated Inhibition of Cue-induced Nicotine Seeking. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 59 p.

Source: Masters Abstracts International, Volume: 80-11.

Thesis (M.A.)--Arizona State University, 2019.

This item must not be sold to any third party vendors.

Nicotine self-administration is associated with decreased expression of the glial glutamate transporter 1 (GLT-1) and the cystine-glutamate exchange protein xCT in the nucleus accumbens core (NAcore). N-acetylcysteine (NAC), which is an antioxidant, anti-inflammatory, and glutamatergic agent, restores these proteins associated with increased relapse vulnerability. However, the specific molecular mechanisms driving NAC inhibitory effects on cue-induced nicotine reinstatement are unknown. Thus, the present study assessed NAC's effects on cue-induced nicotine reinstatement are dependent on NAcore GLT-1 expression. Here, rats were treated with NAC in combination with intra-NAcore vivo-morpholinos to examine the role of GLT-1 in NAC-mediated inhibition of cue-induced nicotine seeking. Subchronic NAC treatment attenuated cue-induced nicotine seeking in male rats and an antisense vivo-morpholino (AS) designed to selectively suppress GLT-1 expression in the NAcore blocked this effect. NAC treatment was also associated with an inhibition of pro-inflammatory tumor necrosis factor alpha (TNFα) expression in the NAcore. As well, GLT-1 AS markedly increased expression of CD40, a known marker of pro-inflammatory M1 activation of microglia and macrophages. To further examine whether NAC-induced decreases in nicotine seeking involve suppression of TNFα, we manipulated a downstream mediator of this pathway, nuclear factor kappa B (NF-kB). Considering the putative role of NF-κB in learning, memory, and synaptic plasticity, separate experiments were performed where rats were treated with herpes simplex virus (HSV) vectors designed to increase (HSV-IKKca) or decrease (HSV-IKKdn) NF-κB signaling through interactions with IκB Kinase (IKK). The goal was to examine the role of NF-κB signaling in mediating nicotine seeking behavior and if NF-κB signaling regulates GLT-1 expression. HSV-IKKdn alone and in combination with NAC inhibited cue-induced nicotine reinstatement, while HSV-IKKca blocked the attenuating effect of NAC on reinstatement. Interestingly, both HSV-IKKdn and HSV-IKKca, regardless of NAC treatment, inhibited GLT-1 expression. Taken together, these results suggest that while GLT-1 may be a conserved neurobiological substrate underlying relapse vulnerability across drugs of abuse, immunomodulatory mechanisms may regulate drug-induced alterations in glutamatergic plasticity that mediate cue-induced drug-seeking behavior through GLT-1-independent mechanisms.

ISBN: 9781392129869Subjects--Topical Terms:

588700
Neurosciences.

Glutamatergic and Neuroimmune Mechanisms of N-acetylcysteine-mediated Inhibition of Cue-induced Nicotine Seeking.
LDR:03606nmm a2200337 4500 001 2207266
005 20190916101811.5
008 201008s2019 ||||||||||||||||| ||eng d
020 $a 9781392129869
035 $a (MiAaPQ)AAI13806032
035 $a (MiAaPQ)asu:18576
035 $a AAI13806032
040 $a MiAaPQ $c MiAaPQ
100 1 $a Namba, Mark Douglas. $3 3434231
245 1 0 $a Glutamatergic and Neuroimmune Mechanisms of N-acetylcysteine-mediated Inhibition of Cue-induced Nicotine Seeking.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2019
300 $a 59 p.
500 $a Source: Masters Abstracts International, Volume: 80-11.
500 $a Publisher info.: Dissertation/Thesis.
500 $a Advisor: Gipson-Reichardt, Cassandra D.
502 $a Thesis (M.A.)--Arizona State University, 2019.
506 $a This item must not be sold to any third party vendors.
520 $a Nicotine self-administration is associated with decreased expression of the glial glutamate transporter 1 (GLT-1) and the cystine-glutamate exchange protein xCT in the nucleus accumbens core (NAcore). N-acetylcysteine (NAC), which is an antioxidant, anti-inflammatory, and glutamatergic agent, restores these proteins associated with increased relapse vulnerability. However, the specific molecular mechanisms driving NAC inhibitory effects on cue-induced nicotine reinstatement are unknown. Thus, the present study assessed NAC's effects on cue-induced nicotine reinstatement are dependent on NAcore GLT-1 expression. Here, rats were treated with NAC in combination with intra-NAcore vivo-morpholinos to examine the role of GLT-1 in NAC-mediated inhibition of cue-induced nicotine seeking. Subchronic NAC treatment attenuated cue-induced nicotine seeking in male rats and an antisense vivo-morpholino (AS) designed to selectively suppress GLT-1 expression in the NAcore blocked this effect. NAC treatment was also associated with an inhibition of pro-inflammatory tumor necrosis factor alpha (TNFα) expression in the NAcore. As well, GLT-1 AS markedly increased expression of CD40, a known marker of pro-inflammatory M1 activation of microglia and macrophages. To further examine whether NAC-induced decreases in nicotine seeking involve suppression of TNFα, we manipulated a downstream mediator of this pathway, nuclear factor kappa B (NF-kB). Considering the putative role of NF-κB in learning, memory, and synaptic plasticity, separate experiments were performed where rats were treated with herpes simplex virus (HSV) vectors designed to increase (HSV-IKKca) or decrease (HSV-IKKdn) NF-κB signaling through interactions with IκB Kinase (IKK). The goal was to examine the role of NF-κB signaling in mediating nicotine seeking behavior and if NF-κB signaling regulates GLT-1 expression. HSV-IKKdn alone and in combination with NAC inhibited cue-induced nicotine reinstatement, while HSV-IKKca blocked the attenuating effect of NAC on reinstatement. Interestingly, both HSV-IKKdn and HSV-IKKca, regardless of NAC treatment, inhibited GLT-1 expression. Taken together, these results suggest that while GLT-1 may be a conserved neurobiological substrate underlying relapse vulnerability across drugs of abuse, immunomodulatory mechanisms may regulate drug-induced alterations in glutamatergic plasticity that mediate cue-induced drug-seeking behavior through GLT-1-independent mechanisms.
590 $a School code: 0010.
650 4 $a Neurosciences. $3 588700
650 4 $a Pharmacology. $3 634543
650 4 $a Behavioral Sciences. $3 789898
690 $a 0317
690 $a 0419
690 $a 0602
710 2 $a Arizona State University. $b Psychology. $3 1677434
773 0 $t Masters Abstracts International $g 80-11.
790 $a 0010
791 $a M.A.
792 $a 2019
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13806032