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Opioidergic Modulation of Ethanol Self-Administration in the Ventral Pallidum

Authors

  • Heidi Kemppainen,

    1. From the Department of Alcohol, Drugs and Addiction (HK, NR, VS-Y, KK), National Institute for Health and Welfare, Helsinki, Finland.
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  • Noora Raivio,

    1. From the Department of Alcohol, Drugs and Addiction (HK, NR, VS-Y, KK), National Institute for Health and Welfare, Helsinki, Finland.
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  • Ville Suo-Yrjo,

    1. From the Department of Alcohol, Drugs and Addiction (HK, NR, VS-Y, KK), National Institute for Health and Welfare, Helsinki, Finland.
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  • Kalervo Kiianmaa

    1. From the Department of Alcohol, Drugs and Addiction (HK, NR, VS-Y, KK), National Institute for Health and Welfare, Helsinki, Finland.
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Reprint requests: Kalervo Kiianmaa, PhD, Department of Alcohol, Drugs and Addiction, National Institute for Health and Welfare, POB 30, 00271 Helsinki, Finland; Tel.: +538 20 610 8111; Fax: +358 20 610 6111; E-mail: kalervo.kiianmaa@thl.fi

Abstract

Background:  Striatopallidal medium spiny neurons have been viewed as a final common path for drug reward and the ventral pallidum as an essential convergent point for hedonic and motivational signaling in the brain. The medium spiny neurons are GABAergic, but they colocalize enkephalin. Purpose of this study was to investigate the role of the opioidergic mechanisms of the ventral pallidum in ethanol self-administration behavior.

Methods:  Effects of bilateral microinjections of μ-, δ-, and κ-opioid receptor agonists and antagonists into the ventral pallidum on voluntary ethanol consumption were monitored in alcohol-preferring Alko Alcohol (AA) rats using the 90-minute limited access paradigm.

Results:  Stimulation of μ-opioid receptors with DAMGO (0.01 to 0.1 μg) or morphine (1 to 10 μg) in the ventral pallidum decreased ethanol intake dose-dependently. Conversely, blocking μ-receptors with CTOP (0.3 to 3 μg) increased ethanol intake significantly. Unlike CTOP, DAMGO also increased locomotor activity. Consumption of ethanol was not modified significantly by a broad-spectrum opioid receptor antagonist naltrexone, by δ-opioid receptor agonist DPDPE or antagonist naltrindole, or by a κ-opioid receptor agonist U50,488H or antagonist nor-BNI.

Conclusions:  The study provides evidence for μ- but not δ- or κ-opioid receptors in the ventral pallidum playing a role in the regulation of voluntary ethanol consumption. Furthermore, present findings give support to earlier work, suggesting an essential role of pallidal opioidergic transmission in drug reward.

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