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Nicotine as a modulator of behavior: beyond the inverted U
Abstract
Nicotine is the crucial component in tobacco that underlies smoking behavior; however, the effects of nicotine can vary in both human and animal studies. Recent data from knockout mouse studies, neurotransmitter release studies and electrophysiological experiments support the hypothesis that conflicting behavioral effects elicited by nicotine can result from the activation of different subtypes of nicotinic acetylcholine receptors and the stimulation of antagonistic neuronal pathways. Thus, small differences in the activation state, connectivity or sensitivity of neuronal pathways among individuals might result in large differences in behavioral responses to nicotine. An understanding of the molecular and cellular processes that oppose nicotine reinforcement will be crucial for the development of new interventions to initiate smoking cessation or to prevent the transition from occasional smoking to dependence.
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“The result of this circuit-level integration is that nicotine can modulate behavioral function bidirectionally, acting as a stimulant and increasing anxiety under some conditions and decreasing activity and anxiety in others (Picciotto 2003).”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Picciotto 2003
In the citing paper
“nAChRs are expressed throughout the brain on both excitatory and inhibitory neurons, with the ability to increase inhibition of circuits when excitation is high and to increase excitation when circuits are less active (Picciotto 2003).”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Picciotto 2003
In the citing paper
“Nicotine follows an inverted U-shaped dose-response curve [18, 60], and smokers titrate their nicotine intake to experience the rewarding while avoiding the aversive effects produced by high nicotine doses [61–64].”
From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [60]
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Metadata
- Authors
- Picciotto, M. R.
- Affiliations
- Yale University (US)
- Corresponding author
- Picciotto, Marina R
- ORCID
- Picciotto, Marina R
- Venue
- Trends in Pharmacological Sciences
- Publisher
- Elsevier BV
- Published
- 2003-09
- Volume
- 24
- Issue
- 9
- Pages
- 493-499
- ISSN
- 0165-6147 (ISSN-L)
- OpenAlex
- W2049324875
- Cited by
- 257
- References
- 79
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 6 · 2023: 12 · 2022: 2 · 2021: 9 · 2020: 15 · 2019: 6 · 2018: 5 · 2017: 8 · 2016: 9 · 2015: 8 · 2014: 13 · 2013: 15 · 2012: 14
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Pharmacological Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (DA14241, DA 10455, DA84733, DA 00436)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- nicotine, nicotinic acetylcholine receptors, receptor subtypes, nicotine reinforcement, smoking behavior, nicotine dependence, smoking cessation, neural pathways, knockout mice, neurotransmitter release, electrophysiology
- MeSH terms
- Animals, Behavior, Humans, Nicotine, Receptors, Nicotinic, Smoking, Nicotinic Agonists, Mice
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