Enkephalin, PPE mRNA, and PTS-1 in alcohol withdrawal seizure-prone and -resistant mice.
Inbred animal strains provide an opportunity to study genetic factors in alcoholism in the absence of environmental factors. Although the concentration of methionine enkephalin (Met-enkephalin) in whole brain has been implicated in the consumption of ethanol, it has not been studied in the brains of alcohol withdrawal seizure-prone (WSP) and withdrawal seizure-resistant (WSR) mice. We compared these concentrations with the levels of preproenkephalin (PPE) mRNA and with the activity of peptide transport system-1 (PTS-1), a brain-to-blood transport system for Met-enkephalin that is affected by ethanol. The concentrations of Met-enkephalin were significantly greater in WSP mice than in WSR mice, whereas synthesis of Met-enkephalin, as reflected by PPE mRNA levels, and transport out of the brain by PTS-1 was not different. These results support a direct link between elevated concentrations of Met-enkephalin in whole brain and proneness to withdrawal-induced seizures. We suggest that the inverse relationship between the consumption of ethanol and proneness to seizures in inbred mice can be explained through their opposite relationships to Met-enkephalin.
Plotkin
S R
SR
Tulane Neuroscience Interdisciplinary Program, Veterans Affairs Medical Center, New Orleans, LA 70146, USA.
Banks
W A
WA
Kastin
A J
AJ
D000818:Animals; D004744:Enkephalin, Methionine / Q000378:metabolism*; D004745:Enkephalins / Q000235:genetics*; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012640:Seizures / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000150:complications* / Q000378:metabolism
D004745:Enkephalins; D026901:Membrane Transport Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D000431:Ethanol; D004744:Enkephalin, Methionine; C033660:preproenkephalin; C043912:peptide permease