Effect of acute ethanol administration on the release of opioid peptides from the midbrain including the ventral tegmental area

Alcohol Clin Exp Res. 2009 Jun;33(6):1033-43. doi: 10.1111/j.1530-0277.2009.00924.x. Epub 2009 Mar 19.

Abstract

Background: Experimental evidence suggests that ethanol alters the activity of the endogenous opioid peptide systems in a dose and brain-region dependent manner. These alterations may influence the processes of ethanol reward and reinforcement. Thus, it was the objective of this study to investigate the response of the 3 major opioid peptide systems (endorphins, enkephalins, and dynorphins) to acute ethanol administration, at the level of the midbrain including the ventral tegmental area (midbrain/VTA), a region important for drug, including ethanol reinforcement.

Methods: Using the in vivo microdialysis technique coupled with specific solid-phase radioimmunoassay for beta-endorphin, met-enkephalin, and dynorphin A(1-8,) changes in the extracellular concentration of theses peptides at the level of midbrain/VTA were determined at distinct time points following the administration of 0.0 (saline), 0.8, 1.2, 1.6, 2.0, and 2.4 g ethanol/kg B.Wt.

Results: A biphasic effect of ethanol on beta-endorphin release was found, with low to medium (1.2, 1.6, and 2.0 g) but not high (2.4 g) doses of ethanol, inducing a significant increase in the dialysate content of beta-endorphin. A late increase in the dialysate content of dynorphin A(1-8) was observed in response to the 1.2 g ethanol dose. However, none of the ethanol doses tested significantly altered the content of met-enkephalin in the dialysate.

Conclusions: The present findings suggest that the ethanol-induced increase of beta-endorphin release at the level of midbrain/VTA may influence alcohol reinforcement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcoholism / metabolism
  • Animals
  • Central Nervous System Depressants / blood
  • Central Nervous System Depressants / pharmacology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Dynorphins / metabolism
  • Enkephalin, Methionine / metabolism
  • Ethanol / blood
  • Ethanol / pharmacology*
  • Injections, Intraperitoneal
  • Male
  • Mesencephalon / drug effects*
  • Mesencephalon / metabolism*
  • Opioid Peptides / metabolism*
  • Peptide Fragments / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Ventral Tegmental Area / drug effects*
  • Ventral Tegmental Area / metabolism*
  • beta-Endorphin / metabolism

Substances

  • Central Nervous System Depressants
  • Opioid Peptides
  • Peptide Fragments
  • Ethanol
  • Enkephalin, Methionine
  • beta-Endorphin
  • Dynorphins
  • dynorphin (1-8)