Psychopharmacology

, Volume 223, Issue 2, pp 211–221 | Cite as

Role for ventral pallidal GABAergic mechanisms in the regulation of ethanol self-administration

Original Investigation
First Online:
Received:
Accepted:

Abstract

Rationale

The striatopallidal medium spiny neurons have been viewed as a final common path for drug reward, and the ventral pallidum (VP) as a convergent point for hedonic and motivational signaling. The medium spiny neurons are GABAergic, but they colocalize enkephalin.

Objective

The present study investigated the role of the GABAergic mechanisms of the VP in ethanol consumption.

Methods

The effects of bilateral microinjections of GABAA and GABAB receptor agonists and antagonists into the VP on voluntary ethanol consumption were monitored in alcohol-preferring Alko alcohol rats given 90 min limited access to ethanol in their home cages every other day. The influences of coadministration of GABA and opioid receptor modulators were also studied.

Results

The GABAA receptor agonist muscimol (1–10 ng/site) decreased ethanol intake dose-dependently, while administration of the GABAA receptor antagonist bicuculline (10–100 ng) had an opposite effect. The GABAB receptor agonist baclofen (3–30 ng) also suppressed ethanol intake, but the GABAB receptor antagonist saclofen (0.3–3 μg) failed to modify it. Animals coadministered with bicuculline (30 ng) and baclofen (30 ng) consumed ethanol significantly less than those treated with bicuculline alone. Coadministration of the μ-receptor agonist D-Ala2,N-Me-Phe4,Glyol5-enkephalin (DAMGO, 0.1 μg) with bicuculline counteracted, whereas the μ-receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP, 1 μg) enhanced the bicuculline-induced increase of ethanol intake. When given alone, DAMGO decreased while CTOP increased ethanol intake.

Conclusions

The study provides evidence for the ventral pallidal GABAergic mechanisms participating in the regulation of ethanol consumption and supports earlier work suggesting a role for pallidal opioidergic transmission in ethanol reward.

Keywords

Ventral pallidum GABA Ethanol intake Microinjection Opioid Addiction 
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Notes

Acknowledgments

This paper was supported by grants from the Academy of Finland and the Finnish Foundation for Alcohol Studies. We thank Ms. Leena Tanner-Väisänen for her technical assistance.

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Heidi Kemppainen
    • 1
  • Noora Raivio
    • 1
  • Kalervo Kiianmaa
    • 1
  1. 1.Department of Alcohol, Drugs and AddictionNational Institute for Health and WelfareHelsinkiFinland

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