Journal article
Chronic treatment with N-acetylcysteine decreases extinction responding and reduces cue-induced nicotine-seeking
Physiological reports, v 7(1), e13958
Jan 2019
PMID: 30632301
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
N-acetylcysteine (NAC), a promising glutamatergic therapeutic agent, has shown some clinical efficacy in reducing nicotine use in humans and has been shown to reverse drug-induced changes in glutamatergic neurophysiology. In rats, nicotine-seeking behavior is associated with alterations in glutamatergic plasticity within the nucleus accumbens core (NAcore). Specifically, cue-induced nicotine-seeking is associated with rapid, transient synaptic plasticity (t-SP) in glutamatergic synapses on NAcore medium spiny neurons. The goal of the present study was to determine if NAC reduces nicotine-seeking behavior and reverses reinstatement-associated NAcore glutamatergic alterations. Rats were extinguished from nicotine self-administration, followed by subchronic NAC administration (0 or 100 mg/kg/d) for 4 days prior to cue-induced reinstatement. NAcore synaptic potentiation was measured via dendritic spine morphology and mRNA and protein of relevant glutamatergic genes were quantified. Nicotine-seeking behavior was not reduced by subchronic NAC treatment. Also, NAcore transcript and protein expression of multiple glutamatergic genes, as well as spine morphological measures, were unaffected by subchronic NAC. Finally, chronic NAC treatment (15 days total) during extinction and prior to reinstatement significantly decreased extinction responding and reduced reinstatement of nicotine-seeking compared to vehicle. Together, these results suggest that chronic NAC treatment is necessary for its therapeutic efficacy as a treatment strategy for nicotine addiction and relapse.
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Details
- Title
- Chronic treatment with N-acetylcysteine decreases extinction responding and reduces cue-induced nicotine-seeking
- Creators
- Gregory L Powell - Arizona State UniversityJonna M Leyrer-Jackson - Arizona State UniversityJulianna Goenaga - Arizona State UniversityMark D Namba - Arizona State UniversityJose Piña - Arizona State UniversitySade Spencer - Medical University of South CarolinaNeringa Stankeviciute - Medical University of South CarolinaDanielle Schwartz - Medical University of South CarolinaNicholas P Allen - Lake Erie College of Osteopathic MedicineArmani P Del Franco - University of MinnesotaErin A McClure - Medical University of South CarolinaMichael Foster Olive - Arizona State UniversityCassandra D Gipson - Arizona State University
- Publication Details
- Physiological reports, v 7(1), e13958
- Grant note
- R00 DA041462 / NIDA NIH HHS DA036569 / NIH HHS DA044479 / NIH HHS DA036569-S1 / NIH HHS DA045881 / NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000456090500017
- Scopus ID
- 2-s2.0-85059829808
- Other Identifier
- 991021955155004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Physiology