Primary reinforcing effects of nicotine are triggered from multiple regions both inside and outside the ventral tegmental area
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Nicotine is thought to be the key substance responsible for tobacco-smoking habits and appears to trigger reinforcement via the ventral tegmental area (VTA). Recently, multiple anatomical substrates for drug reinforcement have been identified in the vicinity of the ventral midbrain. In addition to the posterior portion of the VTA, the central linear nucleus raphé and the supramammillary nucleus of the posterior hypothalamus mediate drug reinforcement. Using intracranial self-administration procedures, we examined whether these regions mediate the reinforcing effects of nicotine. Rats learned to lever press for self-administration of nicotine into the posterior VTA, central linear nucleus, and supramammillary nucleus, suggesting a reinforcing action of nicotine in these regions. The rats did not self-administer nicotine into surrounding regions including the anterior VTA, substantia nigra, the region just dorsal to the posterior VTA, interpeduncular nucleus, or medial mammillary nucleus. The reinforcing effects of nicotine into the three brain regions were further confirmed by a two-lever discrimination procedure, in which rats learned to selectively respond between active and inactive levers. The reinforcing effects of nicotine administration into the posterior VTA, central linear nucleus, and supramammillary nucleus were blocked by coadministration of the nicotine receptor antagonist mecamylamine. The reinforcing effects of nicotine into the posterior VTA or central linear nucleus were attenuated by coadministration of the D2 receptor agonist quinpirole. These findings demonstrate that nicotine reinforcement involves multiple regions both inside and outside the VTA.
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Local infusion of nicotine into the VTA has much greater effects on locomotion and self-administration than local infusion into the NAc.
“local infusion of nicotine into the VTA has much greater effects on locomotion and self-administration than local infusion into the NAc (Ferrari et al., 2002; Ikemoto et al., 2006).”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Ikemoto et al., 2006
Drugs such as nicotine and opiates are more rewarding when administered into the posterior VTA or the central linear nucleus than into the anterior VTA.
“Drugs such as nicotine and opiates are more rewarding when administered into the posterior VTA or the central linear nucleus than into the anterior VTA.”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Ikemoto et al., 2006
Rats learn to lever-press for administration of drugs such as nicotine, carbachol, opiates, cannabinoids, cocaine, ethanol and its metabolite acetaldehyde into the posterior VTA more readily than into the anterior VTA.
“Rats learn to lever-press for administration of drugs such as nicotine (Ikemoto et al., 2006), carbachol (Ikemoto and Wise, 2002), opiates (Zangen et al., 2002), cannabinoids (Zangen et al., 2006), cocaine (Rodd et al., 2005), ethanol (Rodd-Henricks et al., 2000) and its metabolite acetaldehyde (Rodd et al., 2004) into the posterior VTA more readily than into the anterior VTA.”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Ikemoto et al., 2006
The central (or caudal) linear nucleus raphe, localized posterodorsal to the VTA, is involved in drug reward.
“In addition to the posterior VTA, the central (or caudal) linear nucleus raphe, localized posterodorsal to the VTA, is involved in drug reward.”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Ikemoto et al., 2006
Rats learn to self-administer nicotine and other drugs into the central linear nucleus.
“Rats learn to self-administer nicotine and other drugs into the central linear nucleus”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Ikemoto et al., 2006
Rats learn to self-administer the excitatory amino acid AMPA or nicotine into the supramammillary nucleus, localized just anteromedial to the anterior VTA and dorsal to the mammillary body.
“It was found that rats learn to self-administer the excitatory amino acid AMPA or nicotine into the supramammillary nucleus (Ikemoto et al., 2004; 2006), localized just anteromedial to the anterior VTA and dorsal to the mammillary body”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Ikemoto et al., 2006
Other drugs of abuse such as nicotine and opiates appear to act in the posteromedial VTA and central linear nucleus.
“Other drugs of abuse such as nicotine and opiates appear to act in the posteromedial VTA and central linear nucleus.”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Ikemoto et al., 2006
Rats do not learn to self-administer AMPA or nicotine into the anterior VTA.
“Importantly, they do not learn to self-administer these drugs into the anterior VTA.”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Ikemoto et al., 2006
Rats quickly learn to self-administer nicotine or the GABAA receptor agonist muscimol into the central linear nucleus.
“The central linear nucleus, into which rats quickly learn to self-administer nicotine or the GABAA receptor agonist muscimol (Ikemoto et al., 1998; Ikemoto et al., 2006), provides heavy dopaminergic inputs to the ventromedial striatum.”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Ikemoto et al., 2006
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- Authors
- Ikemoto, S., Qin, M., & Liu, Z.-H.
- Affiliations
- National Institutes of Health (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2006-01-18
- Volume
- 26
- Issue
- 3
- Pages
- 723-730
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC1380251
- OpenAlex
- W2081997259
- Cited by
- 151
- References
- 40
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 6 · 2019: 1 · 2018: 8 · 2017: 5 · 2016: 3 · 2015: 9 · 2014: 12 · 2013: 12 · 2012: 9
- FWCI
- 4.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (Z01DA000439)
- 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
- nicotine, drug reinforcement, ventral tegmental area, supramammillary nucleus, posterior hypothalamus, mecamylamine, nicotinic acetylcholine receptors, dopamine D2 receptor, quinpirole, smoking
- MeSH terms
- Animals, Discrimination Learning, Dopamine, Male, Nicotine, Reinforcement, Psychology, Self Administration, Rats, Wistar, Ventral Tegmental Area, Dopamine Antagonists, Rats
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