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Conditioned and sensitized responses to stimulant drugs in humans
Abstract
In animal models considerable evidence suggests that increased motivation to seek and ingest drugs of abuse are related to conditioned and sensitized activations of the mesolimbic dopamine (DA) system. Direct evidence for these phenomena in humans, though, is sparse. However, recent studies support the following. First, the acute administration of drugs of abuse across pharmacological classes increases extracellular DA levels within the human ventral striatum. Second, individual differences in the magnitude of this response correlate with rewarding effects of the drugs and the personality trait of novelty seeking. Third, transiently diminishing DA transmission in humans decreases drug craving, the propensity to preferentially respond to reward-paired stimuli, and the ability to sustain responding for future drug reward. Finally, very recent studies suggest that repeated exposure to stimulant drugs, either on the street or in the laboratory, can lead to conditioned and sensitized behavioral responses and DA release. In contrast to these findings, though, in individuals with a long history of substance abuse, drug-induced DA release is decreased. This diminished DA release could reflect two different phenomena. First, it is possible that drug withdrawal related decrements in DA cell function persist longer than previously suspected. Second, drug-paired stimuli may gain marked conditioned control over the release of DA and the expression of sensitization leading to reduced DA release when drug-related cues are absent. Based on these observations a two-factor hypothesis of the role of DA in drug abuse is proposed. In the presence of drug cues, conditioned and sensitized DA release would occur leading to focused drug-seeking behavior. In comparison, in the absence of drug-related stimuli DA function would be reduced, diminishing the ability of individuals to sustain goal-directed behavior and long-term objectives. This conditioned control of the expression of sensitized DA release could aggravate susceptibility to relapse, narrow the range of interests and perturb decision-making, accounting for a wide range of addiction related phenomena.
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In the citing paper
“These experience-dependent mechanisms regulate the sensitivity and plasticity of the central nervous system and act at several biological levels (likely partly in parallel with each other): i) cellular changes such as neurogenesis, pruning and sprouting of synapses, myelination of axons and alterations to the number of dendritic spines9, 10, ii) subcellular changes, such as alterations to the”
From Resilience in mental health: linking psychological and neurobiological perspectives. (2013) · cites this paper as [11]
In the citing paper
“Dependence to drugs of abuse is closely associated with impulsivity, or the propensity to choose a lower, but immediate, reward over a delayed, but more valuable outcome.”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Leyton, 2007
In the citing paper
“One reason for this discrepancy may be explained by the “inverted U” model, which proposes that optimal dopamine transmission, which is neither too low nor too high, is required for optimal response inhibition (Cools and D'Esposito, 2011; Gjedde et al., 2010; Leyton, 2007).”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Leyton, 2007
In the citing paper
“Sensitization of mesolimbic dopamine function results in the amplification of the neural mechanisms for incentive salience that transform ordinary levels of cue-triggered ‘wanting’ into excessive levels of urges to take drugs and gamble, and a persistent vulnerability to relapse (Boileau et al., 2014; W. Y. Kim, Cho, Kwak, & Kim, 2017; Leyton, 2007).”
In the citing paper
“This finding implies that while gambling-related cues take on increased incentive salience, other non-related or unfamiliar cues may become less important or even inhibit motivation (Leyton, 2007; 2014; Leyton & Vezina, 2012; 2014).”
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Metadata
- Authors
- Leyton, M.
- Affiliations
- McGill University (CA)
- Corresponding author
- Leyton, Marco
- ORCID
- Leyton, Marco
- Venue
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2007-11
- Volume
- 31
- Issue
- 8
- Pages
- 1601-1613
- ISSN
- 0278-5846 (ISSN-L)
- OpenAlex
- W1991899916
- Cited by
- 127
- References
- 197
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 4 · 2022: 2 · 2021: 8 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 2 · 2016: 8 · 2015: 6 · 2014: 14 · 2013: 14 · 2012: 16
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- McGill University
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- sensitization, mesolimbic dopamine system, dopamine release, ventral striatum, drug craving, novelty seeking, drug reward, relapse, drug withdrawal, stimulants, addiction, goal-directed behavior
- MeSH terms
- Central Nervous System Stimulants, Behavior, Conditioning, Psychological, Cues, Dopamine, Humans, Substance-Related Disorders
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