Opioidergic Modulation of Ethanol Self-Administration in the Ventral Pallidum

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 mu-, delta-, and kappa-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 mu-opioid receptors with DAMGO (0.01 to 0.1 mu g) or morphine (1 to 10 mu g) in the ventral pallidum decreased ethanol intake dose-dependently. Conversely, blocking mu-receptors with CTOP (0.3 to 3 mu g) 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 delta-opioid receptor agonist DPDPE or antagonist naltrindole, or by a kappa-opioid receptor agonist U50,488H or antagonist nor-BNI. Conclusions: The study provides evidence for mu- but not delta- or kappa-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.