D1 and D2 dopamine receptor function in the striatum: coactivation of D1- and D2-dopamine receptors on separate populations of neurons results in potentiated immediate early gene response in D1-containing neurons
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D1- and D2-dopamine receptor-mediated regulation of immediate early gene levels in identified populations of neurons in the striatum was examined with quantitative in situ hybridization histochemical techniques. Levels of messenger RNA (mRNA) encoding the immediate early genes zif268 and c-fos were examined in two experiments in rats with unilateral lesions of the nigrostriatal dopamine pathway. In a dose- response study, animals were treated with doses of 0.5, 1.0, and 1.5 mg/kg of the D1 agonist SKF-38393 either alone or in combination with the D2 agonist quinpirole (1 mg/kg). Levels of immediate early gene mRNAs 60 min following drug treatments showed a dose-related increase to the D1 agonist alone and a potentiation to combined D1 and D2 against treatment. In a second experiment, in animals receiving 1 mg/kg SKF-38393 either alone or in combination with 1 mg/kg quinpirole, the level of zif268 mRNA was measured with a double-labeling method in striatal neurons containing enkephalin mRNA, a marker of D2-containing neurons, and in neurons not containing enkephalin, putative D1- containing neurons. In the dopamine-depleted striatum, D1 agonist treatment alone did not affect enkephalin-positive neurons but significantly elevated zif268 mRNA levels in nearly all enkephalin- negative neurons. Combined D1 and D2 agonist treatment further increased zif268 mRNA levels in this population of enkephalin-negative neurons and decreased zif-268 mRNA levels in enkephalin-positive neurons. These data indicate that the synergistic response to combined D1- and D2-receptor stimulation is mediated by interneuronal interactions involving the activation of D1 and D2 receptors on separate populations of striatal neurons.
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Under normal conditions, a synergistic balance of D1R- and D2R-like activation exists in striatal regions.
“Under normal conditions, a synergistic balance of D1R- and D2R-like activation exists in striatal regions (Walters et al 1987; LaHoste et al 1993; Gerfen et al 1995; Wise et al 1996; Hu and White 1997).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Gerfen et al 1995
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- Authors
- Gerfen, C., Keefe, K., & Gauda, E.
- Affiliations
- National Institutes of Health (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1995-12-01
- Volume
- 15
- Issue
- 12
- Pages
- 8167-8176
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6577952
- OpenAlex
- W2097919380
- Cited by
- 283
- References
- 35
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 12 · 2015: 11 · 2014: 6 · 2013: 6 · 2012: 11
- FWCI
- 5.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- dopamine D1 receptor, dopamine D2 receptor, striatum, immediate early genes, Zif268, c-fos, enkephalin, nigrostriatal dopamine pathway, SKF 38393, quinpirole, receptor coactivation
- MeSH terms
- Animals, Corpus Striatum, DNA-Binding Proteins, Dose-Response Relationship, Drug, Male, Neurons, RNA, Messenger, Transcription Factors, Gene Expression, Genes, fos, Rats, Sprague-Dawley, Receptors, Dopamine D1, Receptors, Dopamine D2, Genes, Immediate-Early, Immediate-Early Proteins, Dopamine Agonists, Rats, Early Growth Response Protein 1
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