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Cited by 87Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchSchizophrenia research and treatment

Characterization of dopamine D1 and D2 receptor function in socially housed cynomolgus monkeys self-administering cocaine

Czoty, PaulW., Morgan, Drake, Shannon, ErinE., Gage, H.Donald, Nader, MichaelA.·2004·Psychopharmacology
DOI 10.1007/s00213-003-1752-z
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Abstract

Rationale Social rank has been shown to influence dopamine (DA) D(2) receptor function and vulnerability to cocaine self-administration in cynomolgus monkeys. The present studies were designed to extend these findings to maintenance of cocaine reinforcement and to DA D(1) receptors.Objective Examine the effects of a high-efficacy D(1) agonist on an unconditioned behavior (eyeblinking) and a low-efficacy D(1) agonist on cocaine self-administration, as well as the effects of cocaine exposure on D(2) receptor function across social ranks, as determined by positron emission tomography (PET).Methods Effects of the high-efficacy D(1) agonist SKF 81297 and cocaine (0.3-3.0 mg/kg) on spontaneous blinking were characterized in eight monkeys during 15-min observation periods. Next, the ability of the low-efficacy D(1) agonist SKF 38393 (0.1-17 mg/kg) to decrease cocaine self-administration (0.003-0.1 mg/kg per injection, IV) was assessed in 11 monkeys responding under a fixed-ratio 50 schedule. Finally, D(2) receptor levels in the caudate and putamen were assessed in nineteen monkeys using PET.Results SKF 81297, but not cocaine, significantly increased blinking in all monkeys, with slightly greater potency in dominant monkeys. SKF 38393 dose-dependently decreased cocaine-maintained response rates with similar behavioral potency and efficacy across social rank. After an extensive cocaine self-administration history, D(2) receptor levels did not differ across social ranks.Conclusions These results suggest that D(1) receptor function is not substantially influenced by social rank in monkeys from well-established social groups. While an earlier study showed that dominant monkeys had higher D(2) receptor levels and were less sensitive to the reinforcing effects of cocaine during initial exposure, the present findings indicate that long-term cocaine use changed D(2) receptor levels such that D(2) receptor function and cocaine reinforcement were not different between social ranks. These findings suggest that cocaine exposure attenuated the impact of social housing on DA receptor function.

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  • Animals with low D2 receptor levels in the striatum before drug or alcohol exposure subsequently display greater cocaine or alcohol self-administration.

    “Strikingly, animals with low D2 receptor levels in the striatum prior to drug or alcohol exposure subsequently display greater cocaine or alcohol self-administration (Czoty et al., 2004; Dalley et al., 2007; McBride et al., 1993; Morgan et al., 2002; Nader et al., 2006; Stefanini et al., 1992).”

    From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Czoty et al., 2004

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Authors
Czoty, P., Morgan, D., Shannon, E., Gage, H. D., & Nader, M.
Affiliations
Wake Forest University Health Sciences (US)
ORCID
Gage, H.Donald
Venue
Psychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2004-02-07
Volume
174
Issue
3
Pages
381-8
ISSN
  • 0033-3158 (ISSN-L)
  • 1432-2072
DOI
10.1007/s00213-003-1752-z
OpenAlex
W2139294399
Cited by
87
References
53
Citations by year
2026: 1 · 2025: 3 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 24 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 7 · 2013: 3 · 2012: 6
FWCI
1.05
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 (DA10584)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Keywords
dopamine D1 receptor, dopamine D2 receptor, cocaine self-administration, social rank, social dominance, Macaca fascicularis, SKF 81297, SKF 38393, cocaine reinforcement, caudate nucleus, putamen, fixed-ratio schedules
MeSH terms
Analysis of Variance, Animals, Behavior, Animal, Benzamides, Benzazepines, Blinking, Cocaine, Conditioning, Operant, Dose-Response Relationship, Drug, Drug Interactions, Hierarchy, Social, Macaca fascicularis, Male, Piperidines, Self Administration, Tissue Distribution, Tomography, Emission-Computed, Neostriatum, Receptors, Dopamine D1, Receptors, Dopamine D2, Dopamine Agonists, Dopamine Uptake Inhibitors

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