Cited by 384Neuropeptides and Animal PhysiologyNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

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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.

Devine, D P, Leone, P, Pocock, D, Wise, R A·1993·The Journal of Pharmacology and Experimental Therapeutics

DOI 10.1016/s0022-3565(25)39324-9

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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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Authors: Devine, D. P., Leone, P., Pocock, D., & Wise, R. A.
Affiliations: Concordia University (CA)
ORCID: Devine, D P
Leone, P
Wise, R A
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)
DOI: 10.1016/s0022-3565(25)39324-9
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
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

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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.

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