Effects of intranucleus accumbens shell administration of dopamine agonists and antagonists on cocaine-taking and cocaine-seeking behaviors in the rat
Abstract
Rationale Dopamine signaling in the nucleus accumbens (NAc) plays an important role in regulating drug-taking and drug-seeking behaviors, but the role of D(1)- and D(2)-like receptors in this regulation remains unclear.Objectives Our objective was to study the role of NAc D(1)- and D(2)-like receptors in the reinstatement of cocaine-seeking behavior and the regulation of stabilized cocaine intake in rats.Methods Using a within-session reinstatement procedure, whereby animals self-administer cocaine (90 min) and extinguish responding (150 min) in a single session, we assessed the ability of NAc microinfusions of the D(1) agonist SKF 81297 and the D(2) agonist 7-OH-DPAT to reinstate extinguished cocaine seeking. The effects of the D(1) antagonist SCH 23390 and the D(2) antagonist eticlopride pretreatment on agonist- and cocaine-primed reinstatement were also measured. Similar agonist and antagonist treatments were tested for their ability to modulate stabilized cocaine and sucrose self-administration.Results Intra-NAc infusions of either SKF 81297 (0.3-3.0 microg) or 7-OH-DPAT (1.0-10.0 microg) dose-dependently reinstated cocaine seeking with greater efficacy in the medial core than in the shell subregion and at doses that also stimulated locomotor behavior. Intra-NAc shell infusions of SCH 23390 (1.0 microg) and eticlopride (3.0-10.0 microg) blocked cocaine-primed reinstatement (2.0 mg/kg, i.v.) and indiscriminately blocked reinstatement induced by either intra-NAc D(1) or D(2) agonists. Doses of agonists that triggered reinstatement failed to alter stabilized cocaine intake, whereas doses of antagonists that blocked reinstatement increased cocaine intake in the shell.Conclusions Both D(1) and D(2) receptors in the NAc play a prominent, and perhaps cooperative, role in regulating cocaine-taking and cocaine-seeking behaviors.
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If cocaine is administered with D2R-like antagonists, it loses its reinforcing effects.
“Furthermore, if cocaine is administered with D2R-like antagonists, it loses its reinforcing effects (Woolverton and Virus 1989; Bachtell et al 2005; Claytor et al 2006; Peng et al 2009).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Bachtell et al 2005
In cocaine reinstatement models, systemic administration of cocaine reinstates conditioned responding, and this cocaine-induced reinstatement is blocked by administration of dopamine receptor antagonists into the medial shell, but not the core.
“For instance, in animals that have extinguished conditioned responding (lever-pressing), systemic administration of cocaine reinstates the conditioned responding, and this cocaine-induced reinstatement is blocked by the administration of dopamine receptor antagonists into the medial shell, but not the core (McFarland and Kalivas, 2001; Anderson et al., 2003; Bachtell et al., 2005; Anderson et al.,”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Bachtell et al., 2005
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- Authors
- Bachtell, R. K., Whisler, K., Karanian, D., & Self, D. W.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Self, David W.
- Venue
- Psychopharmacology
- Published
- 2005-09-15
- Volume
- 183
- Issue
- 1
- Pages
- 41-53
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2130332398
- Cited by
- 154
- References
- 71
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 6 · 2017: 12 · 2016: 3 · 2015: 10 · 2014: 10 · 2013: 11 · 2012: 18
- FWCI
- 3.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (DA 08227, DA10460, F32DA018481, DA 18481, P01DA008227)
- 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
- nucleus accumbens shell, cocaine self-administration, cocaine-seeking behavior, reinstatement, dopamine D1 receptor, dopamine D2 receptor, dopamine agonists, dopamine antagonists, SKF 81297, 7-OH-DPAT, SCH 23390, eticlopride, sucrose self-administration, locomotor activity
- MeSH terms
- Animals, Benzazepines, Cocaine, Dose-Response Relationship, Drug, Male, Motor Activity, Nucleus Accumbens, Salicylamides, Self Administration, Tetrahydronaphthalenes, Time Factors, Rats, Sprague-Dawley, Receptors, Dopamine D1, Receptors, Dopamine D2, Dopamine Agonists, Dopamine Antagonists, Dopamine Uptake Inhibitors, Cocaine-Related Disorders, Rats
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