title: Endogenous opioids are involved in the genetically determined high preference for ethanol consumption.
abstract: The link between endogenous opioid peptides and the genetic predisposition to preferentially consume ethanol was examined in alcohol preferring C57BL/6J mice compared with the alcohol nonpreferring DBA/2 mice. Concentrations of Met-enkephalin pentapeptide or precursor in various brain regions of potential relevance were not different between the two strains. C57BL/6J mice had a significantly lower pain threshold that could be increased by a selective mu-receptor opioid agonist [D-Ala2, MePhe4, Met(O)5-ol]-enkephalin. Treatment with this drug also decreased ethanol consumption in C57BL/6J mice. Increasing the synaptic half-life of endogenous enkephalins by the enkephalinase inhibitor kelatorphan also decreased ethanol consumption. Assay of endogenous enkephalin degrading activity showed increased enkephalinase activity in striatal issue of C57BL/6J compared with DBA/2 tissue. These results suggest that a relative lack of enkephalin peptides trans-synaptically, possibly resulting from enhanced enkephalin degradation may contribute to increase alcohol consumption in C57BL/6J mice.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: S R
authors.initials: SR
authors.lastname: George
authors.forename: L
authors.initials: L
authors.lastname: Roldan
authors.forename: A
authors.initials: A
authors.lastname: Lui
authors.forename: C A
authors.initials: CA
authors.lastname: Naranjo
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D004723:Endorphins / Q000502:physiology*; D004744:Enkephalin, Methionine / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D015260:Neprilysin / Q000378:metabolism; D010147:Pain Measurement; D011863:Radioimmunoassay; D011957:Receptors, Opioid / Q000378:metabolism; D017450:Receptors, Opioid, mu
chemical_list: D004723:Endorphins; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D004744:Enkephalin, Methionine; D015260:Neprilysin