Withdrawal from alcohol in withdrawal seizure-prone and -resistant mice: Evidence for enkephalin resistance

Scott R. Plotkin, William A. Banks, Claudia S. Cohn, Abba J. Kastin

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Methionine enkephalin (Met-enkephalin) functions as an endogenous anticonvulsant. Peptide transport system-1 (PTS-1) is an important regulator of Met-enkephalin levels in brain and transports the peptide from brain to blood. In outbred mice, alcohol dependence is associated with decreased PTS-1 activity and increased levels of Met-enkephalin. In contrast, alcohol withdrawal is associated with recovery of PTS-1 activity, decreased levels of Met-enkephalin, and seizures. In this study, we examined the PTS-1/Met-enkephalin system in two replicates of withdrawal seizure-resistant (WSR) and withdrawal seizure-prone (WSP) mouse lines. We measured levels of preproenkephalin (PPE) mRNA and Met-enkephalin peptide in brain and the activity of PTS-1 during alcohol-naive, -dependent, and -withdrawal states. In alcohol-naive animals, Met-enkephalin levels were higher in WSP than in WSR mice. In alcohol-withdrawal animals, Met-enkephalin levels remained elevated in WSP mice, whereas they increased in WSR mice. Peptide levels were unrelated to levels of PPE mRNA or activity of PTS-1. Factorial analysis showed that proneness to seizures was genetically linked to Met-enkephalin levels in alcohol-naive, -dependent, and -withdrawing mice but not to mRNA levels or PTS-1 activity. Overall, these results may be explained by resistance to enkephalin in WSP mice and suggest that the dysregulation of the PTS-1/Met-enkephalin system contributes to susceptibility to seizures in WSP mice.

Original languageEnglish (US)
Pages (from-to)379-387
Number of pages9
JournalPharmacology Biochemistry and Behavior
Volume68
Issue number3
DOIs
StatePublished - May 29 2001

Keywords

  • Alcoholism
  • Blood-brain barrier
  • Ethanol
  • Genetics
  • Preproenkephalin

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