Role of anterior insula cortex in context-induced relapse of nicotine-seeking
- Medical University of Innsbruck, Austria
- Amsterdam University Medical Centers, Netherlands
- Vrije Universiteit Amsterdam, Netherlands
- University of New South Wales, Australia
Abstract
Tobacco use is the leading cause of preventable death worldwide, and relapse during abstinence remains the critical barrier to successful treatment of tobacco addiction. During abstinence, environmental contexts associated with nicotine use can induce craving and contribute to relapse. The insular cortex (IC) is thought to be a critical substrate of nicotine addiction and relapse. However, its specific role in context-induced relapse of nicotine-seeking is not fully known. In this study, we report a novel rodent model of context-induced relapse to nicotine-seeking after punishment-imposed abstinence, which models self-imposed abstinence through increasing negative consequences of excessive drug use. Using the neuronal activity marker Fos we find that the anterior (aIC), but not the middle or posterior IC, shows increased activity during context-induced relapse. Combining Fos with retrograde labelling of aIC inputs, we show projections to aIC from contralateral aIC and basolateral amygdala exhibit increased activity during context-induced relapse. Next, we used fiber photometry in aIC and observed phasic increases in aIC activity around nicotine-seeking responses during self-administration, punishment, and the context-induced relapse tests. Next, we used chemogenetic inhibition in both male and female rats to determine whether activity in aIC is necessary for context-induced relapse. We found that chemogenetic inhibition of aIC decreased context-induced nicotine-seeking after either punishment- or extinction-imposed abstinence. These findings highlight the critical role nicotine-associated contexts play in promoting relapse, and they show that aIC activity is critical for this context-induced relapse following both punishment and extinction imposed abstinence.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 1-5, and Supplementary Figures 1-3.
Article and author information
Author details
Huibert D Mansvelder
Funding
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (016.Vidi.188.022)
- Nathan J Marchant
Fulbright Association
- Rae J Herman
Austrian Science Fund (SPIN supportW1206-12)
- Hussein Ghareh
- Gerald Zernig
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: In compliance with Dutch law and Institutional regulations, all animal procedures were approved by the Centrale Commissie Dierproeven (CCD) and conducted in accordance with the Experiments on Animal Act. Experiments were approved by the local animal welfare body Animal Experiments Committee of the Vrije Universiteit, Amsterdam, The Netherlands.
Copyright
© 2022, Ghareh et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Role of anterior insula cortex in context-induced relapse of nicotine-seeking
eLife 11:e75609.
https://doi.org/10.7554/eLife.75609
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