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

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.

• Authors: S R Plotkin, W A Banks, C S Cohn, A J Kastin
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 68 Issue 3 Pg. 379-87 (Mar 2001) ISSN: 0091-3057 [Print] United States
• PMID: 11325389 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Central Nervous System Depressants
• Enkephalins
• Neuropeptides
• Protein Precursors
• RNA, Messenger
• Ethanol
• Enkephalin, Methionine
• tyrosyl-prolyl-leucyl-glycinamide
• MSH Release-Inhibiting Hormone
• preproenkephalin
• Aluminum
• Digoxigenin

Topics

• Aluminum (pharmacology)
• Animals
• Brain Chemistry (drug effects, physiology)
• Central Nervous System Depressants
• Digoxigenin (metabolism)
• Enkephalin, Methionine (metabolism)
• Enkephalins (biosynthesis, genetics, physiology)
• Ethanol
• Female
• Half-Life
• MSH Release-Inhibiting Hormone (analogs & derivatives, metabolism)
• Mice
• Mice, Inbred Strains
• Neuropeptides (analysis)
• Protein Precursors (biosynthesis, genetics)
• RNA, Messenger (biosynthesis)
• Radioimmunoassay
• Seizures (genetics, physiopathology)
• Substance Withdrawal Syndrome (physiopathology)