Role of insular cortex D1 and D2 dopamine receptors in nicotine self-administration in rats
Open accessAbstract
The insular cortex has been associated with the processing of rewarding stimuli and with the neural bases of drug addiction. Ischemic damage to the insula has been associated with decreased desire to smoke cigarettes. Which component of insular function is involved in the neural basis of cigarette smoking is not clear. Dopamine systems are crucial for the reinforcing value of addictive drugs. The DA projection from the ventral tegmental area to the nucleus accumbens (NAc) has been shown to be a vital pathway for the primary reinforcement caused by taking a variety of abused drugs. In the current set of studies, the roles of D₁ and D₂ receptors in the insular cortex in the self-administration of nicotine by rats were assessed. Adult female Sprague-Dawley rats were fitted with jugular catheters and given access to self-administer nicotine. Bilateral local infusion cannulae were implanted into the agranular insular cortex to locally administer D₁ and D₂ antagonists (SCH-23390 and haloperidol). Acute local infusions of the D₁ antagonist SCH-23390 into the insula (1-2 μg/side) significantly decreased nicotine self-administration by more than 50%. Repeated infusions of SCH-23390 into the agranular insula caused continuing decreases in nicotine self-administration without signs of tolerance. In contrast, local infusions of the D₂ antagonist haloperidol 0.5-2 μg/side did not have any discernable effect on nicotine self-administration. These studies show the importance of DA D₁ systems in the insula for nicotine reward.
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Blockade of dopamine D1, but not D2, receptors in the aAgIC attenuates nicotine taking.
“Attenuation of nicotine taking is also observed following blockade dopamine D1, but not D2, receptors in the aAgIC”
From The Insula: A Brain Stimulation Target for the Treatment of Addiction (2019) · cites this paper as Kutlu et al., 2013
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- [32]Levin ED Johnson J Slade S Wells C Cauley M Petro A Lorcaserin decreases nicotine self-administration in female rats Journal of Pharmacology and Experimental Therapeutics 2011 338 890 6 21636655 PMC3164341
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The Insula: A Brain Stimulation Target for the Treatment of Addiction
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- Authors
- Kutlu, M. G., Burke, D., Slade, S., Hall, B. J., Rose, J. E., & Levin, E. D.
- Affiliations
- Duke Medical Center (US)
- Corresponding author
- Levin, Edward D.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 256
- Pages
- 273-278
- ISSN
- 0166-4328 (ISSN-L)
- PMC
- PMC3874126
- OpenAlex
- W2055174308
- Cited by
- 41
- References
- 39
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 2 · 2021: 1 · 2019: 7 · 2018: 6 · 2017: 3 · 2016: 3 · 2015: 6 · 2014: 3
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse of the National Institutes of Health (DA027840)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- insula, dopamine D1 receptor, dopamine D2 receptor, nicotine self-administration, nicotine reward, dopamine antagonists, SCH 23390, haloperidol, tobacco dependence, local infusion, drug reinforcement
- MeSH terms
- Animals, Benzazepines, Cerebral Cortex, Dose-Response Relationship, Drug, Female, Haloperidol, Nicotine, Self Administration, Time Factors, Tobacco Use Disorder, Rats, Sprague-Dawley, Receptors, Dopamine D1, Receptors, Dopamine D2, Dopamine Antagonists, Nicotinic Agonists, Dopamine D2 Receptor Antagonists
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