A psychobiological framework of the substrates that mediate nicotine use during adolescence

O'Dell, Laura E.

doi:10.1016/j.neuropharm.2008.07.039

Cited by 81Smoking Behavior and CessationNicotinic Acetylcholine Receptors StudyNeurotransmitter Receptor Influence on Behavior

A psychobiological framework of the substrates that mediate nicotine use during adolescence

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O'Dell, Laura E.·2009·Neuropharmacology

DOI 10.1016/j.neuropharm.2008.07.039PMC PMC2634831

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Abstract

Adolescents are especially likely to initiate tobacco use and are more vulnerable to long-term nicotine dependence. A unifying hypothesis is proposed based largely on animals studies that adolescents, as compared to adults, experience enhanced short-term positive and reduced aversive effects of nicotine, as well as less negative effects during nicotine withdrawal. Thus, during adolescence the strong positive effects of nicotine are inadequately balanced by negative effects that contribute to nicotine dependence in adults. This review provides a neural framework to explain developmental differences within the mesolimbic pathway based on the established role of dopamine in addiction. This pathway originates in the ventral tegmental area (VTA) and terminates in the nucleus accumbens (NAcc) where dopamine is increased by nicotine but decreased during withdrawal. During adolescence, excitatory glutamatergic systems that facilitate dopamine are overdeveloped, whereas inhibitory GABAergic systems are underdeveloped. Thus, it is hypothesized that adolescents display enhanced nicotine reward and reduced withdrawal via enhanced excitation and reduced inhibition of VTA cell bodies that release dopamine in the NAcc. Although this framework focuses on adolescents and adults, it may also apply to the understanding of enhanced vulnerability to nicotine in adults that were previously exposed to nicotine during adolescence. The hypothesis presented in this review suggests that the clinical diagnostic criteria developed for nicotine dependence in adults, based primarily on withdrawal, may be inappropriate during adolescence when nicotine withdrawal does not appear to play a major role in nicotine use. Furthermore, treatment strategies involving nicotine replacement may be harmful for adolescents because it may cause enhanced vulnerability to nicotine dependence later in adulthood.

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At a system level, this might contribute to differences in acute rewarding effects of nicotine and might underlie increased sensitivity of adolescents.
“At a system level, this might contribute to differences in the acute rewarding effects of nicotine, and might underlie the increased sensitivity of adolescents (5, 51).”
From Adolescent nicotine exposure transiently increases high-affinity nicotinic receptors and modulates inhibitory synaptic transmission in rat medial prefrontal cortex (2012) · cites this paper as [5]

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Nicotine in adolescence freezes dopamine circuits in an immature statePreprint
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Adolescent rats are resistant to adaptations in excitatory and inhibitory mechanisms that modulate mesolimbic dopamine during nicotine withdrawal
Natividad, L. A., Buczynski, M. W., Parsons, L. H., Torres, O. V., & O’Dell, L. E. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07926.x · Cited by 24 · see citing works
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Authors: O'Dell, L. E.
Venue: Neuropharmacology
Publisher: Elsevier BV
Published: 2009-01
Volume: 56
Pages: 263-278
ISSN: 0028-3908 (ISSN-L)
DOI: 10.1016/j.neuropharm.2008.07.039
PMC: PMC2634831
OpenAlex: W2105511929
Cited by: 81
References: 168
Citations by year: 2026: 2 · 2025: 1 · 2024: 1 · 2022: 4 · 2021: 8 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 6 · 2015: 6 · 2014: 9 · 2013: 9 · 2012: 10
FWCI: 0.51
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuropharmacology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
scholarworks - UTEP (The University of Texas at El Paso) (submittedVersion)
Funders: National Institute on Drug Abuse (R01DA021274, R25DA033613)
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: adolescent nicotine use, nicotine dependence, mesolimbic dopamine system, ventral tegmental area, nucleus accumbens, nicotine reward, nicotine withdrawal, glutamatergic excitation, GABAergic inhibition, developmental neuroscience, nicotine replacement therapy, tobacco initiation, addiction vulnerability
MeSH terms: Adolescent, Age Factors, Animals, Brain Chemistry, Disease Models, Animal, Dopamine, gamma-Aminobutyric Acid, Humans, Nicotine, Nucleus Accumbens, Tobacco Use Disorder, Ventral Tegmental Area, Nicotinic Agonists

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A psychobiological framework of the substrates that mediate nicotine use during adolescence

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