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Research ArticleNeuropharmacology

Salsolinol Stimulates Dopamine Neurons in Slices of Posterior Ventral Tegmental Area Indirectly by Activating μ-Opioid Receptors

Guiqin Xie, Lucia Hipólito, Wanhong Zuo, Ana Polache, Luis Granero, Krešimir Krnjević and Jiang-Hong Ye
Journal of Pharmacology and Experimental Therapeutics April 2012, 341 (1) 43-50; DOI: https://doi.org/10.1124/jpet.111.186833
Guiqin Xie
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Lucia Hipólito
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Wanhong Zuo
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Ana Polache
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Luis Granero
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Krešimir Krnjević
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Jiang-Hong Ye
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Abstract

Previous studies in vivo have shown that salsolinol, the condensation product of acetaldehyde and dopamine, has properties that may contribute to alcohol abuse. Although opioid receptors, especially the μ-opioid receptors (MORs), may be involved, the cellular mechanisms mediating the effects of salsolinol have not been fully explored. In the current study, we used whole-cell patch-clamp recordings to examine the effects of salsolinol on dopamine neurons of the ventral tegmental area (VTA) in acute brain slices from Sprague-Dawley rats. Salsolinol (0.01–1 μM) dose-dependently and reversibly increased the ongoing firing of dopamine neurons; this effect was blocked by naltrexone, an antagonist of MORs, and gabazine, an antagonist of GABAA receptors. We further showed that salsolinol reduced the frequency without altering the amplitude of spontaneous GABAA receptor-mediated inhibitory postsynaptic currents in dopamine neurons. The salsolinol-induced reduction was blocked by both naltrexone and [d-Ala2,N-Me-Phe4,Gly5-ol]enkephalin, an agonist of MORs. Thus, salsolinol excites VTA-dopamine neurons indirectly by activating MORs, which inhibit GABA neurons in the VTA. This form of disinhibition seems to be a novel mechanism underlying the effects of salsolinol.

Footnotes

  • This work was supported by the National Institutes of Health National Institute on Alcohol Abuse and Alcoholism [Grants AA016964, AA016618] (to J.-H.Y.).

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    http://dx.doi.org/10.1124/jpet.111.186833.

  • ABBREVIATIONS:

    NAcc
    nucleus accumbens
    APV
    2-amino-5-phosphono-valeric acid
    DAMGO
    [d-Ala2,N-Me-Phe4,Gly5-ol]enkephalin
    DNQX
    6,7-dinitroquinoxaline-2,3-dione
    MOR
    μ-opioid receptor
    VTA
    ventral tegmental area
    p-VTA
    posterior VTA
    TTX
    tetrodotoxin
    ACSF
    artificial cerebrospinal fluid
    IPSC
    inhibitory postsynaptic current
    sIPSC
    spontaneous IPSC
    mIPSC
    miniature IPSC
    eIPSC
    evoked IPSC
    HPC
    hyperpolarizing current
    PPR
    paired-pulse ratio
    SAL
    salsolinol
    APs
    action potentials
    GABAR
    GABA receptor
    SR-95531
    2-(3-carboxypropyl)-3-amino-6-(4-methoxyphenyl)pyridazinium bromide.

  • Received August 16, 2011.
  • Accepted December 22, 2011.
  • Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 341 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 341, Issue 1
1 Apr 2012
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Research ArticleNeuropharmacology

Salsolinol Stimulates Dopamine Neurons

Guiqin Xie, Lucia Hipólito, Wanhong Zuo, Ana Polache, Luis Granero, Krešimir Krnjević and Jiang-Hong Ye
Journal of Pharmacology and Experimental Therapeutics April 1, 2012, 341 (1) 43-50; DOI: https://doi.org/10.1124/jpet.111.186833

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Research ArticleNeuropharmacology

Salsolinol Stimulates Dopamine Neurons

Guiqin Xie, Lucia Hipólito, Wanhong Zuo, Ana Polache, Luis Granero, Krešimir Krnjević and Jiang-Hong Ye
Journal of Pharmacology and Experimental Therapeutics April 1, 2012, 341 (1) 43-50; DOI: https://doi.org/10.1124/jpet.111.186833
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