Opposite Modulation of Cocaine-Seeking Behavior by D 1 - and D 2 -Like Dopamine Receptor Agonists
Abstract
Activation of the mesolimbic dopamine system is known to trigger relapse in animal models of cocaine-seeking behavior. We found that this “priming” effect was selectively induced by D 2 -like, and not by D 1 -like, dopamine receptor agonists in rats. Moreover, D 1 -like receptor agonists prevented cocaine-seeking behavior induced by cocaine itself, whereas D 2 -like receptor agonists enhanced this behavior. These results demonstrate an important dissociation between D 1 - and D 2 -like receptor processes in cocaine-seeking behavior and support further evaluation of D 1 -like receptor agonists as a possible pharmacotherapy for cocaine addiction.
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Chronic cocaine exposure is associated with decreases in tonic D2R signaling involved in drug withdrawal, compulsive intake, and reinstatement of drug-seeking behavior.
“The same chronic cocaine exposure is associated with decreases in tonic D2R signaling, and these decreases are involved in drug withdrawal, compulsive intake, and reinstatement of drug-seeking behavior (Nestler et al 1990; Self et al 1996; Perez et al 2011; Grieder et al 2012).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Self et al 1996
Chronic cocaine exposure is associated with increased phasic D1R signaling involved in reward prediction, sensitized reward responses, and dampening further reinforcing effects of drugs of abuse.
“Chronic exposure to cocaine is associated with an increase in phasic D1R signaling, and these increases are involved in reward prediction, sensitized responses to reward, and in dampening further reinforcing effects of drugs of abuse (Ljungberg et al 1992; Henry and White 1995; Self et al 1996; Anderson et al 2008; Bertran-Gonzalez et al 2008; Zweifel et al 2009).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Self et al 1996
Cocaine seeking behavior is inhibited by pharmacological D1R activation, suggesting that experimental D1R activation may reduce the drive to seek out rewards.
“Furthermore, cocaine seeking behavior is inhibited by pharmacological D1R activation (Self et al 1996), suggesting that this experimental activation of D1R may reduce the drive to seek out rewards.”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Self et al 1996
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- Authors
- Self, D. W., Barnhart, W. J., Lehman, D. A., & Nestler, E. J.
- Affiliations
- Yale University (US)
- Corresponding author
- Self, David W.
- Venue
- Science
- Published
- 1996-03-15
- Volume
- 271
- Issue
- 5255
- Pages
- 1586-1589
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2077707065
- Cited by
- 492
- References
- 33
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 6 · 2021: 5 · 2020: 8 · 2019: 5 · 2018: 4 · 2017: 8 · 2016: 9 · 2015: 8 · 2014: 11 · 2013: 15 · 2012: 20
- FWCI
- 14.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- cocaine-seeking behavior, D1-like receptors, D2-like receptors, dopamine agonists, mesolimbic dopamine system, relapse, cocaine dependence, pharmacotherapy, cocaine priming
- MeSH terms
- Animals, Behavior, Animal, Benzazepines, Caffeine, Cocaine, Ergolines, Male, Motor Activity, Recurrence, Reinforcement, Psychology, Tetrahydronaphthalenes, Behavior, Addictive, Rats, Sprague-Dawley, Receptors, Dopamine D1, Receptors, Dopamine D2, Dopamine Agonists, Quinpirole, Substance-Related Disorders, Rats
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