Mesolimbic Dopamine and Habenulo-Interpeduncular Pathways in Nicotine Withdrawal
Open accessAbstract
The majority of people who attempt to quit smoking without some assistance relapse within the first couple of weeks, indicating the increased vulnerability during the early withdrawal period. The habenula, which projects via the fasciculus retroflexus to the interpeduncular nucleus, plays an important role in the withdrawal syndrome. Particularly the α2, α5, and β4 subunits of the nicotinic acetylcholine receptor have critical roles in mediating the somatic manifestations of withdrawal. Furthermore, withdrawal from nicotine induces a hypodopaminergic state, but there is a relative increase in the sensitivity to phasic dopamine release that is caused by nicotine. Therefore, acute nicotine re-exposure causes a phasic DA response that more potently reinforces relapse to smoking during the withdrawal period.
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The habenular complex comprises lateral and medial habenular nuclei and is a diencephalic epithalamic structure located ventrally along the dorsal third ventricle.
“The habenular complex, comprising the lateral (LHb) and medial (MHb) nuclei, is a diencephalic, epithalamic structure located ventrally along the dorsal third ventricle (Dani and De Biasi 2013).”
From Nicotine Withdrawal (2015) · cites this paper as Dani and De Biasi 2013
The Dopamine Systems section says the lateral and medial habenula form the habenula complex, an epithalamic structure by the third ventricle. It does not specify that the complex lies ventrally along the dorsal third ventricle; that more precise location is unsupported by this passage. No page number is provided in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe LHb sends excitatory glutamatergic projections to the RMTg and is a major component of the circuit underlying negative reward.
“The LHb sends excitatory glutamatergic projections to the RMTg and is a major component of the circuit underlying negative reward (Dani and De Biasi 2013).”
From Nicotine Withdrawal (2015) · cites this paper as Dani and De Biasi 2013
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- Authors
- Dani, J. A., & De Biasi, M.
- Affiliations
- Baylor College of Medicine (US)
- ORCID
- Dani, J. A.
- Venue
- Cold Spring Harbor Perspectives in Medicine
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2013-06-01
- Volume
- 3
- Issue
- 6
- Pages
- a012138-a012138
- ISSN
- 2157-1422 (ISSN-L)
- PMC
- PMC3662347
- OpenAlex
- W2120506746
- Cited by
- 34
- References
- 143
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 2 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 5 · 2015: 6 · 2014: 6 · 2013: 1
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Perspectives in Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Prevention and Research Institute of Texas
- Diana Helis Henry Medical Research Foundation
- National Institutes of Health (CA148127, DA09411, NS21229)
- National Institute on Drug Abuse (R21DA029157, DA09411, DA017173, R01DA017173, R01DA009411, DA029157)
- National Cancer Institute (CA148127, U19CA148127)
- National Institute of Neurological Disorders and Stroke (NS 21229, R37NS021229, R01NS021229)
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- nicotine withdrawal, habenula, interpeduncular nucleus, mesolimbic dopamine system, nicotinic acetylcholine receptor subunits, phasic dopamine release, smoking relapse, hypodopaminergic state
- MeSH terms
- Animals, Behavior, Animal, Dopamine, Humans, Limbic System, Nicotine, Receptors, Nicotinic, Reinforcement, Psychology, Substance Withdrawal Syndrome, Signal Transduction, Nicotinic Agonists, Habenula
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