Sensitization of midbrain dopamine neuron reactivity and the self-administration of psychomotor stimulant drugs

Vezina, Paul

doi:10.1016/j.neubiorev.2003.11.001

Cited by 515Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchNeural and Behavioral Psychology Studies

Sensitization of midbrain dopamine neuron reactivity and the self-administration of psychomotor stimulant drugs

Vezina, Paul·2004·Neuroscience & Biobehavioral Reviews

DOI 10.1016/j.neubiorev.2003.11.001

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Abstract

Psychostimulant drugs like amphetamine are readily self-administered by humans and laboratory animals by virtue of their actions on dopamine (DA) neurons in the midbrain. Exposing animals to this drug either systemically or in the cell body region of these neurons in the ventral tegmental area leads to long-lasting alterations in dopaminergic function. These have most often been assessed as increased locomotor activity and enhanced DA overflow in the nucleus accumbens (NAcc) after re-exposure to the drug weeks to months later. Evidence is presented showing that manipulations that produce this sensitization of midbrain DA neuron reactivity enhance the pursuit and self-administration of psychostimulant drugs. Procedures known to prevent the induction of sensitization by amphetamine also prevent the facilitation of drug taking. Enhanced drug self-administration and primed reinstatement of drug seeking are also accompanied by enhanced NAcc DA reactivity. Finally, drugs that increase NAcc DA overflow acutely but fail to produce sensitization of this effect are not associated with the subsequent enhancement of self-administration. These results indicate a direct relationship between the sensitization of midbrain dopamine neuron reactivity and the excessive pursuit and self-administration of psychostimulant drugs. Understanding the neuronal events and adaptations that underlie the induction and expression of sensitization may thus help elucidate how drug abuse develops, how it is reinstated and ultimately how both may be prevented.

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Following repeated exposure to drugs of abuse, 'wanting' and desire for more drug progressively increases.
“In particular, following repeated exposure to drugs of abuse, which progressively increases ‘wanting’ and desire for more drug (Vezina, 2004; Vezina, Lorrain, Arnold, Austin, & Suto, 2002), individuals tend to escalate their consumption by increasing both the frequency with which drug is taken and the quantity consumed during each drug-taking episode.”
From Cued for Risk: Evidence for an Incentive Sensitization Framework to Explain the Interplay between Stress and Anxiety, Substance Abuse, and Reward Uncertainty in Disordered Gambling Behavior (2019) · cites this paper as Vezina, 2004
Sensitization can be seen as a greater behavioral response to the drug or enhanced acquisition and escalation of drug self-administration, that accompany brain neural adaptations that underlie amplified 'wanting' for the reward.
“Sensitization can also be seen as a greater behavioral response to the drug or enhanced acquisition and escalation of drug self-administration, that accompany brain neural adaptations that underlie amplified ‘wanting’ for the reward (Ferrario et al., 2005; Ferrario & Robinson, 2007; Vezina, 2004; Vezina et al., 2002).”
From Cued for Risk: Evidence for an Incentive Sensitization Framework to Explain the Interplay between Stress and Anxiety, Substance Abuse, and Reward Uncertainty in Disordered Gambling Behavior (2019) · cites this paper as Vezina, 2004

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Authors: Vezina, P.
Affiliations: University of Chicago (US)
Corresponding author: Vezina, Paul
Venue: Neuroscience & Biobehavioral Reviews
Publisher: Elsevier BV
Published: 2004-01
Volume: 27
Issue: 8
Pages: 827-839
ISSN: 0149-7634 (ISSN-L)
DOI: 10.1016/j.neubiorev.2003.11.001
OpenAlex: W2044600697
Cited by: 515
References: 118
Citations by year: 2026: 3 · 2025: 7 · 2024: 3 · 2023: 10 · 2022: 15 · 2021: 5 · 2020: 16 · 2019: 9 · 2018: 19 · 2017: 23 · 2016: 26 · 2015: 24 · 2014: 34 · 2013: 28 · 2012: 23
FWCI: 2.42
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience & Biobehavioral Reviews (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01da009860-04)
U.S. Public Health Service
National Institute on Drug Abuse (R01DA009397, DA-9860, DA-9397)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords: midbrain dopaminergic neurons, amphetamine, ventral tegmental area, drug-seeking behavior, reinstatement of drug seeking, locomotor activity, drug addiction, substance use prevention
MeSH terms: Amphetamine, Central Nervous System Stimulants, Animals, Behavior, Animal, Dopamine, Locomotion, Mesencephalon, Neurons, Self Administration, Time Factors

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Sensitization of midbrain dopamine neuron reactivity and the self-administration of psychomotor stimulant drugs

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