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Journal article
Accumbens neuroimmune signaling and dysregulation of astrocytic glutamate transport underlie conditioned nicotine-seeking behavior
Addiction biology, v 25(5), 12797
Sep 2020
PMID: 31330570
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Nicotine self-administration is associated with decreased expression of the glial glutamate transporter (GLT-1) and the cystine-glutamate exchange protein xCT within the nucleus accumbens core (NAcore).N-acetylcysteine (NAC) has been shown to restore these proteins in a rodent model of drug addiction and relapse. However, the specific molecular mechanisms driving its inhibitory effects on cue-induced nicotine reinstatement are unknown. Here, we confirm that extinction of nicotine-seeking behavior is associated with impaired NAcore GLT-1 function and expression and demonstrates that reinstatement of nicotine seeking rapidly enhances membrane fraction GLT-1 expression. Extinction and cue-induced reinstatement of nicotine seeking was also associated with increased tumor necrosis factor alpha (TNF alpha) and decreased glial fibrillary acidic protein (GFAP) expression in the NAcore. NAC treatment (100 mg/kg/day, i.p., for 5 d) inhibited cue-induced nicotine seeking and suppressed AMPA to NMDA current ratios, suggesting that NAC reduces NAcore postsynaptic excitability. In separate experiments, rats received NAC and an antisense vivo-morpholino to selectively suppress GLT-1 expression in the NAcore during extinction and were subsequently tested for cue-induced reinstatement of nicotine seeking. NAC treatment rescued NAcore GLT-1 expression and attenuated cue-induced nicotine seeking, which was blocked by GLT-1 antisense. NAC also reduced TNF alpha expression in the NAcore. Viral manipulation of the NF-kappa B pathway, which is downstream of TNF alpha, revealed that cue-induced nicotine seeking is regulated by NF-kappa B pathway signaling in the NAcore independent of GLT-1 expression. Ultimately, these results are the first to show that immunomodulatory mechanisms may regulate known nicotine-induced alterations in glutamatergic plasticity that mediate cue-induced nicotine-seeking behavior.
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Details
- Title
- Accumbens neuroimmune signaling and dysregulation of astrocytic glutamate transport underlie conditioned nicotine-seeking behavior
- Creators
- Mark D. Namba - Arizona State UniversityYonatan M. Kupchik - Hebrew University of JerusalemSade M. Spencer - University of MinnesotaConstanza Garcia-Keller - Medical University of South CarolinaJulianna G. Goenaga - Arizona State UniversityGregory L. Powell - Arizona State UniversityIan A. Vicino - Arizona State UniversityIan B. Hogue - Arizona State UniversityCassandra D. Gipson - Arizona State University
- Publication Details
- Addiction biology, v 25(5), 12797
- Publisher
- Wiley
- Number of pages
- 13
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000560421700010
- Scopus ID
- 2-s2.0-85069713764
- Other Identifier
- 991021955786004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Substance Abuse