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Differential involvement of ventral tegmental mu, delta and kappa opioid receptors in modulation of basal mesolimbic dopamine release: in vivo microdialysis studies.
Abstract
In vivo microdialysis was used to assess the involvement of ventral tegmental area (VTA) mu, delta, and kappa opioid receptors in modulation of basal extracellular ventral striatal dopamine (DA) and DA-metabolite concentrations. Independent groups of chloral hydrate-anesthetized rats were given VTA microinjections of selective opioid agonists, and extracellular ventral striatal DA and DA-metabolite concentrations were assayed using HPLC. VTA microinjections of [D-Ala2, N-Me-Phe4-Gly5-ol]-enkephalin (DAMGO; a mu agonist) and [D-Pen2, D-Pen5]-enkephalin (DDDPE; a delta agonist) each caused dose-orderly increases in ventral striatal DA and DA-metabolite concentrations. The effective concentrations of DPDPE were 100- to 1000-fold higher than the effective concentrations of DAMGO. VTA microinjections of (trans-(dl)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclo-hexyl]- benzeneacetamide) methane sulfonate hydrate (U-50,488H); a kappa agonist) failed to alter ventral striatal DA concentrations at any dose tested, but subsequent systemic injections significantly decreased DA and DA-metabolite concentrations. Pretreatment with VTA microinjections of 17-cyclopropylmethyl-6,7-dehydro-4,5-epoxy-3,14-dihydroxy-6,7,2',3'- indolmorphinan hydrochloride (naltrindole; a delta antagonist) (delta antagonist) antagonized VTA DPDPE-mediated increases in ventral striatal DA and DA-metabolite concentrations but failed to antagonize VTA DAMGO-mediated increases. Pretreatment with D-Pen-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP; a mu antagonist) antagonized VTA DAMGO-mediated increases but failed to antagonize VTA DPDPE-mediated increases. Thus both mu and delta receptor agonist appear capable of increasing ventral striatal DA and DA-metabolite concentrations through selective actions on their preferred class of opioid receptors in the VTA. The increases in ventral striatal DA and DA-metabolite concentrations that are seen after systemic treatment with kappa opioid agonists appear not to involve VTA opioid receptors.
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“In particular, dynorphins decrease and enkephalins increase the release of DA (Devine et al. 1993; Di Chiara & Imperato 1988; Longoni et al. 1991; Pentney & Gratton 1991; Spanagel et al. 1990a,b, 1992).”
From Reward, addiction, withdrawal to nicotine (2011) · cites this paper as Devine et al. 1993
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“may reflect known interactions between the dopamine and endorphin systems in both humans and rodents (40, 55, 56), whereby endorphin activation may itself trigger a dopamine response”
From Variation in the β-endorphin, oxytocin, and dopamine receptor genes is associated with different dimensions of human sociality (2017) · cites this paper as [56]
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Metadata
- Authors
- Devine, D. P., Leone, P., Pocock, D., & Wise, R. A.
- Affiliations
- Concordia University (CA)
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1993-07
- Volume
- 266
- Issue
- 3
- Pages
- 1236-1246
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2108098398
- Cited by
- 382
- References
- 0
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 9 · 2020: 8 · 2019: 10 · 2018: 5 · 2017: 10 · 2016: 7 · 2015: 10 · 2014: 7 · 2013: 13 · 2012: 10
- FWCI
- 3.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Funders
- National Institute on Drug Abuse (DA1720)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- ventral tegmental area, mu-opioid receptor, delta opioid receptor, kappa opioid receptor, dopamine release, ventral striatum, dopamine metabolites, DAMGO, DPDPE, U50,488H, naltrindole, CTOP, mesolimbic dopamine system, opioid receptor selectivity, enkephalin, opioid agonists, opioid antagonists
- MeSH terms
- Amino Acid Sequence, Analgesics, Animals, Chromatography, High Pressure Liquid, Corpus Striatum, Dialysis, Dopamine, Enkephalins, Homovanillic Acid, Hydroxyindoleacetic Acid, Limbic System, Male, Microinjections, Molecular Sequence Data, Naltrexone, Narcotic Antagonists, Pyrrolidines, Rats, Inbred Strains, Receptors, Opioid, Tegmentum Mesencephali, 3,4-Dihydroxyphenylacetic Acid, 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer, Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, Enkephalin, D-Penicillamine (2,5)-, Rats
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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