title: Opioidergic modulation of ethanol self-administration in the ventral pallidum.
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.
authors: Department of Alcohol, Drugs and Addiction, National Institute for Health and Welfare, Helsinki, Finland.
authors: Heidi
authors: H
authors: Kemppainen
authors: Noora
authors: N
authors: Raivio
authors: Ville
authors: V
authors: Suo-Yrjo
authors: Kalervo
authors: K
authors: Kiianmaa
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000428:Alcohol Drinking / Q000235:genetics / Q000503:physiopathology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D005917:Globus Pallidus / Q000503:physiopathology*; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D011957:Receptors, Opioid / Q000819:agonists / Q000502:physiology*; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D012646:Self Administration; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; C051844:norbinaltorphimine; D013004:Somatostatin; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; C055382:naltrindole