Cited by 340Neurotransmitter Receptor Influence on BehaviorNeuropeptides and Animal PhysiologyNeuroscience and Neuropharmacology Research

Properties and opioid inhibition of mesolimbic dopamine neurons vary according to target location

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Ford, Christopher P., Mark, Gregory P., Williams, John T.·2006·The Journal of Neuroscience

Abstract

The mesolimbic dopamine system, which mediates the rewarding properties of nearly all drugs of abuse, originates in the ventral tegmental area (VTA) and sends major projections to both the nucleus accumbens (NAc) and the basolateral amygdala (BLA). To address whether differences occur between neurons that project to these separate areas, retrograde microspheres were injected to either the BLA or the NAc of DBA/2J mice. Whole-cell recordings were made from labeled VTA dopamine neurons. We found that identified neurons that projected to the BLA and NAc originated within different quadrants of the VTA with neither group exhibiting large-amplitude h-currents. Neurons that projected to the NAc exhibited a greater outward current in response to the kappa-opioid agonist (5alpha,7alpha,8alpha)-(+)-N-methyl-N-[7-(pyrrolidinyl)-1-oxaspiro [4,5]dec-8-yl]-benzeneacetamide (U69593; 200 nM), whereas neurons that projected to the BLA exhibited greater inhibition to the mu/delta opioid agonist [Met5] enkephalin (ME; 3 microM). In addition, we found that the presynaptic inhibition of GABAergic transmission at both GABAA and GABAB receptors was differentially regulated by U69593 between the two groups. When dopamine IPSCs were examined, U69593 caused a greater inhibition in NAc- than BLA-projecting neurons. ME had no effect on either. Finally, the regulation of extracellular dopamine by dopamine uptake transporters was equal across the VTA. These results suggest that opioids differentially inhibit mesolimbic neurons depending on their target projections. Identifying the properties of projecting mesolimbic VTA dopamine neurons is crucial to understanding the action of drugs of abuse.

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Crossref · 10.1523/jneurosci.4331-05.2006

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Authors
Ford, C. P., Mark, G. P., & Williams, J. T.
Affiliations
Oregon Health & Science University (US)
Venue
The Journal of Neuroscience
Published
2006-03-08
Volume
26
Issue
10
Pages
2788-2797
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2012111567
Cited by
339
References
52
Citations by year
2026: 12 · 2025: 9 · 2024: 7 · 2023: 14 · 2022: 14 · 2021: 8 · 2020: 14 · 2019: 14 · 2018: 10 · 2017: 24 · 2016: 22 · 2015: 26 · 2014: 25 · 2013: 28 · 2012: 21
FWCI
7.20
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
Funders
  • Life Sciences Research Foundation
  • Fondation pour la Recherche Médicale
  • National Institutes of Health
  • National Institute on Drug Abuse (DA04523, DA 014639, R01DA008163, DA-08163, R01DA014639, R01DA004523)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
mesolimbic dopamine system, ventral tegmental area, nucleus accumbens, basolateral amygdala, opioid inhibition, kappa opioid receptor, [Met5]enkephalin, presynaptic inhibition, GABAA receptor, GABAB receptors, retrograde tracing, drug reward
MeSH terms
Amygdala, Analgesics, Animals, Bicuculline, Biotin, Cell Count, Dopamine, Dose-Response Relationship, Radiation, Drug Interactions, Electric Stimulation, Female, Immunohistochemistry, Limbic System, Male, Membrane Potentials, Mice, Inbred DBA, Microinjections, Molecular Sequence Data, Naloxone, Narcotic Antagonists, Narcotics, Neural Inhibition, Neural Pathways, Synaptic Transmission, Neurons, Nucleus Accumbens, Reaction Time, Serotonin, Tyrosine 3-Monooxygenase, Serotonin Receptor Agonists, Ventral Tegmental Area, Patch-Clamp Techniques, GABA Antagonists, Mice, In Vitro Techniques

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