Incubation of nicotine seeking is associated with enhanced protein kinase A-regulated signaling of dopamine- and cAMP-regulated phosphoprotein of 32 kDa in the insular cortex
Open accessAbstract
A recent clinical study demonstrated that damage to the insular cortex can disrupt tobacco addiction. The neurobiological mechanisms for this effect are not yet understood. In this study we used an animal model of nicotine addiction to examine the possibility that changes in insular cortex levels of dopamine (DA)- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), a phosphoprotein enriched in DA neurons containing DA D1 receptors, may be associated with changes in vulnerability to nicotine addiction. Once rats acquired self-administration, they were given unlimited access to nicotine (0.01 mg/kg/infusion) for 23 h/day for a total of 10 days. Each infusion was paired with a visual cue (stimulus light) and auditory cue (sound of pump). Nicotine seeking, as assessed under a cue-induced reinstatement paradigm, and markers of DARPP-32 signaling, as assessed using western blot analysis, were examined in separate groups of rats at two different abstinent intervals: 1 and 7 days. Consistent with findings with other drugs of abuse, rats in the 7-day abstinence group took longer to extinguish and responded at higher levels during reinstatement testing as compared with rats in the 1-day reinstatement group. Relative to saline controls, rats in the 7-day but not the 1-day abstinence group had higher levels of DARPP-32 phosphorylated at the protein kinase A site in the insular cortex. These results demonstrate incubation of drug seeking following extended access to nicotine self-administration and suggest that enhanced protein kinase A signaling in the insular cortex via phosphorylation of DARPP-32 at Thr34 is associated with this effect.
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The incubation of nicotine seeking is associated with higher levels of DARPP-32 in both the aAgIC and pGIC.
“The incubation of nicotine seeking (i.e., greater seeking after 7 days vs. 1 day of abstinence) is associated with higher levels of dopamine (DA)- and cyclic adenosine monophosphate (cAMP)-regulated phosphoprotein of 32 kDa (DARPP-32), enriched in DA neurons containing DA D1 receptors, in both the aAgIC and pGIC”
From The Insula: A Brain Stimulation Target for the Treatment of Addiction (2019) · cites this paper as Abdolahi et al., 2010
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- Authors
- Abdolahi, A., Acosta, G., Breslin, F. J., Hemby, S. E., & Lynch, W. J.
- Affiliations
- University of Virginia (US)
- Wake Forest University Health Sciences (US)
- Corresponding author
- Lynch, Wendy J.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2010-02
- Volume
- 31
- Issue
- 4
- Pages
- 733-741
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- PMC
- PMC3756534
- OpenAlex
- W2053058520
- Cited by
- 110
- References
- 41
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 2 · 2021: 6 · 2020: 5 · 2019: 9 · 2018: 11 · 2017: 6 · 2016: 13 · 2015: 13 · 2014: 7 · 2013: 10 · 2012: 8
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01da024716-13)
- National Institute on Drug Abuse (R01-DA024716)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- nicotine seeking, insula, DARPP-32, protein kinase A signaling, dopamine D1 receptor, nicotine self-administration, cue-induced reinstatement, abstinence, nicotine dependence, dopaminergic neurons
- MeSH terms
- Animals, Cerebral Cortex, Cues, Extinction, Psychological, Male, Nicotine, Nucleus Accumbens, Self Administration, Time Factors, Signal Transduction, Behavior, Addictive, Rats, Sprague-Dawley, Cyclic AMP-Dependent Protein Kinases, Rats, Dopamine and cAMP-Regulated Phosphoprotein 32
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