New concepts in cocaine addiction: The dopamine depletion hypothesis

Dackis, Charles A.; Gold, Mark S.

doi:10.1016/0149-7634(85)90022-3

Cited by 607Neurotransmitter Receptor Influence on BehaviorSubstance Abuse Treatment and OutcomesGambling Behavior and Treatments

New concepts in cocaine addiction: The dopamine depletion hypothesis

Dackis, Charles A., Gold, Mark S.·1985·Neuroscience & Biobehavioral Reviews

DOI 10.1016/0149-7634(85)90022-3

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Abstract

Euphoric properties of cocaine lead to the development of chronic abuse, and appear to involve the acute activation of central DA neuronal systems. This is based upon known effects of cocaine on DA neurons, and the role played by DA in reward states and self-stimulation behavior. With chronic cocaine use, neurotransmitter and neuroendocrine alterations occur. DA depletion is hypothesized to result from overstimulation of these neurons and excessive synaptic metabolism of the neurotransmitter. DA depletion may underlie dysphoric aspects of cocaine abstinence, and cocaine urges. Neurochemical disruptions caused by cocaine are consistent with the concept of "physical" rather than "psychological" addiction. Possible pharmacological interventions in cocaine addiction are outlined and the psychological approach to these patients is discussed.

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Foundational research from the 1970s and 1980s, prior to completion of the Human Genome Project, established dopamine's pivotal role in substance-related pharmacodynamics, including alcohol and cocaine dependence.
“Notably, foundational research from the 1970s and 1980s, prior to completion of the Human Genome Project, established dopamine’s pivotal role in substance-related pharmacodynamics, including alcohol and cocaine dependence.22,23”
From Beyond Stigma–Integrating Neurobiology, Genetics, and Awareness Integration Theory in Addiction Recovery (2026) · cites this paper as [23]

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“22,23 Addiction can be conceptualized as a behavioral choice influenced by competing contingencies, especially sensitivity to immediate (NOW) versus delayed (LATER) rewards.”
Self-citation

Authors: Dackis, C. A., & Gold, M. S.
Affiliations: Summit Oaks Hospital (US)
Corresponding author: Gold, Mark S.
ORCID: Gold, Mark S.
Venue: Neuroscience & Biobehavioral Reviews
Publisher: Elsevier BV
Published: 1985-09
Volume: 9
Issue: 3
Pages: 469-477
ISSN: 0149-7634 (ISSN-L)
DOI: 10.1016/0149-7634(85)90022-3
OpenAlex: W2005239439
Cited by: 607
References: 84
Citations by year: 2026: 4 · 2025: 10 · 2024: 9 · 2023: 15 · 2022: 5 · 2021: 9 · 2020: 7 · 2019: 9 · 2018: 9 · 2017: 17 · 2016: 11 · 2015: 14 · 2014: 18 · 2013: 6 · 2012: 13
FWCI: 2.77
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience & Biobehavioral Reviews (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Social Sciences › Psychology › Clinical Psychology › Gambling Behavior and Treatments
Keywords: cocaine dependence, dopamine depletion, dopaminergic neurons, reward, self-stimulation, cocaine abstinence, cocaine craving, neuroendocrine changes, neurotransmitter metabolism, pharmacotherapy, psychological intervention
MeSH terms: Animals, Brain, Cocaine, Conditioning, Operant, Dopamine, Euphoria, Female, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Male, Models, Neurological, Models, Psychological, Synaptic Transmission, Prolactin, Reward, Serotonin, Substance Withdrawal Syndrome, Thyroid Gland, Thyrotropin-Releasing Hormone, Substance-Related Disorders, Mice, Rats

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New concepts in cocaine addiction: The dopamine depletion hypothesis

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