Effects of dopamine D-1 and D-2 antagonists on cocaine self-administration under different schedules of reinforcement in the rat.
Abstract
The effects of three dopamine D-1 receptor antagonists (SCH23390, SCH39166 and A69024) and three dopamine D-2 antagonists (raclopride, eticlopride and spiperone) on cocaine self-administration maintained under different schedules of reinforcement were examined in the rat. Intravenous cocaine self-administration was maintained under a fixed-ratio (FR) 5 schedule with a 20-sec timeout (TO) after each reinforcement or a FR 15 with a 2-min TO multiple schedule of cocaine (0.25 mg i.v.) and food (45 mg) reinforcement. With the exception of raclopride, all of the antagonists altered the self-administration of cocaine in a manner similar to decreasing the unit dose of cocaine under the schedule in effect, reflected by increased self-administration under the FR 5 TO 20-sec schedule and decreased self-administration under the FR 15 TO 2-min multiple schedule. Moreover, a low dose of either of the benzazepine dopamine D-1 antagonists SCH23390 or SCH39166, but not the other compounds, selectively reduced cocaine self-administration without altering responding for food under the multiple schedule. Conversely, a low dose of raclopride or A69024 selectively decreased food-reinforced responding without altering cocaine self-administration under the multiple schedule. These results suggest that benzazepine dopamine D-1 antagonists, at low doses, may attenuate the reinforcing properties of cocaine more selectively than other dopamine receptor antagonists. The results also demonstrate the advantages of using different schedules to investigate the effects of dopamine D-1 and D-2 antagonists on cocaine self-administration.
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DA receptor antagonists administered systemically increase the rate of operant responding for cocaine in animals.
“By contrast, DA receptor antagonists administered systemically increase the rate of operant responding for cocaine in animals [134-136].”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [134]
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- Authors
- Caine, S. B., & Koob, G. F.
- Affiliations
- Scripps Research Institute (US)
- ORCID
- Koob, G F
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1994-07
- Volume
- 270
- Issue
- 1
- Pages
- 209-218
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W1943544645
- Cited by
- 298
- References
- 0
- Citations by year
- 2024: 3 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 8 · 2019: 7 · 2018: 5 · 2017: 5 · 2016: 9 · 2015: 4 · 2014: 13 · 2013: 5 · 2012: 7
- FWCI
- 3.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Funders
- National Institutes of Health (1f31da005478-01)
- National Institute on Drug Abuse (DA07348, DA 05478, DA04398, R01DA004398)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- cocaine self-administration, SCH 23390, raclopride, eticlopride, spiperone, reinforcement schedules, fixed-ratio schedules, multiple schedules, food reinforcement
- MeSH terms
- Animals, Behavior, Animal, Cocaine, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Interactions, Male, Reinforcement, Psychology, Self Administration, Rats, Wistar, Receptors, Dopamine D1, Rats, Dopamine D2 Receptor Antagonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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