TY - JOUR
T1 - Role of anterior insula cortex in context-induced relapse of nicotine-seeking
AU - Ghareh, Hussein
AU - Alonso-Lozares, Isis
AU - Schetters, Dustin
AU - Herman, Rae J
AU - Heistek, Tim S
AU - Van Mourik, Yvar
AU - Jean-Richard-Dit-Bressel, Philip
AU - Zernig, Gerald
AU - Mansvelder, Huibert D
AU - De Vries, Taco J
AU - Marchant, Nathan J
N1 - Funding Information: The authors gratefully acknowledge the VUmc Histology Imaging Unit for their support & assistance in whole-slide imaging. The authors would like to thank Francesco Ferraguti for insightful comments in the preparation of this manuscript. The work was supported by an NWO VIDI grant (016.Vidi.188.022), Fulbright Fellowship to RH, and Austrian Science Fund (FWF) grant Signal Processing in Neurons (SPIN) W1206-12 to HG and GZ (graduate program Signal Processing In Neurons, https://www. neurospin.at/). The authors declare no conflict of interest.Funder Grant reference number AuthorNederlandse Organisatie voor Wetenschappelijk Onderzoek 016.Vidi.188.022 Nathan J MarchantFulbright Association Rae J HermanAustrian Science Fund Signal Processing in Neurons (SPIN) grant W1206-12 Hussein Ghareh Gerald Zernig. Funding Information: The authors gratefully acknowledge the VUmc Histology Imaging Unit for their support & assistance in whole-slide imaging. The authors would like to thank Francesco Ferraguti for insightful comments in the preparation of this manuscript. The work was supported by an NWO VIDI grant (016.Vidi.188.022), Fulbright Fellowship to RH, and Austrian Science Fund (FWF) grant Signal Processing in Neurons (SPIN) W1206-12 to HG and GZ (graduate program Signal Processing In Neurons, https://www. neurospin.at/). The authors declare no conflict of interest. Publisher Copyright: © Ghareh, Alonso-Lozares et al.
PY - 2022/5/10
Y1 - 2022/5/10
N2 - 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 labeling 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.
AB - 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 labeling 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.
KW - Animals
KW - Extinction, Psychological/physiology
KW - Female
KW - Male
KW - Nicotine/adverse effects
KW - Punishment
KW - Rats
KW - Recurrence
KW - Self Administration
UR - http://www.scopus.com/inward/record.url?scp=85130767642&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85130767642&partnerID=8YFLogxK
U2 - https://doi.org/10.7554/eLife.75609
DO - https://doi.org/10.7554/eLife.75609
M3 - Article
C2 - 35536612
SN - 2050-084X
VL - 11
SP - 1
EP - 27
JO - eLife
JF - eLife
M1 - e75609
ER -