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Research ArticleBehavioral Pharmacology

Synergistic Self-Administration of Ethanol and Cocaine Directly into the Posterior Ventral Tegmental Area: Involvement of Serotonin-3 Receptors

Zheng-Ming Ding, Scott M. Oster, Sheketha R. Hauser, Jamie E. Toalston, Richard L. Bell, William J. McBride and Zachary A. Rodd
Journal of Pharmacology and Experimental Therapeutics January 2012, 340 (1) 202-209; DOI: https://doi.org/10.1124/jpet.111.187245
Zheng-Ming Ding
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Scott M. Oster
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Sheketha R. Hauser
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Jamie E. Toalston
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Richard L. Bell
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William J. McBride
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Zachary A. Rodd
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Abstract

Ethanol (EtOH) and cocaine are both self-administered into the posterior ventral tegmental area (VTA). Self-administration of either drug is prevented by coadministration of a serotonin (5-HT3) receptor antagonist. Electrophysiological studies indicated that cocaine and EtOH can act synergistically to stimulate VTA dopamine neurons. The current experiment assessed whether cocaine and EtOH would synergistically interact to produce a reinforcing action within the posterior VTA. Adult female Wistar rats were randomly assigned to one of 13 groups. There were three control groups: artificial cerebrospinal fluid (aCSF), a subthreshold EtOH (100 mg%) group, and a subthreshold cocaine (25 pmol/100 nl) group. The other groups self-administered 50 or 75 mg% EtOH containing 6.25, 12.5, or 25 pmol/100 nl cocaine or 100 mg% EtOH containing 3.12, 6.25, 12.5, or 25 pmol/100 nl cocaine. All rats received the assigned infusate for sessions 1 through 4, aCSF alone in sessions 5 and 6, and the original infusate during session 7. The effects of adding a 5-HT3 receptor antagonist [tropisetron, C17H20N2O2 (ICS 205,930) and C17H22N4O.C4H4O4 (LY278-584)] on coadministration of EtOH and cocaine (75 mg% + 12.5 pmol/100 nl) were determined. Rats failed to self-administer aCSF or the subthreshold concentration of EtOH or cocaine. All three concentrations of EtOH (50, 75, and 100 mg%) combined with cocaine (12.5 and 25 pmol/100 nl) supported self-administration. Adding a 5HT3 receptor antagonist attenuated coadministration of EtOH + cocaine. Overall, the data indicate that the reinforcing properties of EtOH and cocaine interacted synergistically within the posterior VTA, and these synergistic effects were mediated, at least in part, by activation of local 5-HT3 receptors.

Footnotes

  • This study was supported in part by the National Institutes of Health National Institute of Alcohol Abuse and Alcoholism [Grants AA07462, AA07611, AA12262, AA10721].

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

    http://dx.doi.org/10.1124/jpet.111.187245.

  • ABBREVIATIONS:

    NAC
    nucleus accumbens
    aCSF
    artificial cerebrospinal fluid
    VTA
    ventral tegmental area
    ICS 205,930
    tropisetron, C17H20N2O2
    LY278-584
    C17H22N4O.C4H4O4
    ANOVA
    analysis of variance.

  • Received August 30, 2011.
  • Accepted October 18, 2011.
  • Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 340 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 340, Issue 1
1 Jan 2012
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Research ArticleBehavioral Pharmacology

ICSA of EtOH and Cocaine within the VTA

Zheng-Ming Ding, Scott M. Oster, Sheketha R. Hauser, Jamie E. Toalston, Richard L. Bell, William J. McBride and Zachary A. Rodd
Journal of Pharmacology and Experimental Therapeutics January 1, 2012, 340 (1) 202-209; DOI: https://doi.org/10.1124/jpet.111.187245

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Research ArticleBehavioral Pharmacology

ICSA of EtOH and Cocaine within the VTA

Zheng-Ming Ding, Scott M. Oster, Sheketha R. Hauser, Jamie E. Toalston, Richard L. Bell, William J. McBride and Zachary A. Rodd
Journal of Pharmacology and Experimental Therapeutics January 1, 2012, 340 (1) 202-209; DOI: https://doi.org/10.1124/jpet.111.187245
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