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

doi:10.1016/S0091-3057(00)00480-9

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

Laboratory Medicine and Pathology

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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 language	English (US)
Pages (from-to)	379-387
Number of pages	9
Journal	Pharmacology Biochemistry and Behavior
Volume	68
Issue number	3
DOIs	https://doi.org/10.1016/S0091-3057(00)00480-9
State	Published - 2001

Bibliographical note

Funding Information:
The authors with to thank Melita B. Fasold, Amy Baber, and Gerald Miller for technical assistance; Dr. Charles Ide for supplying the primer sequences for β-actin; Dr. Steven Sabol for supplying the cDNA for PPE; and Dr. John Crabbe for advice. This work was supported by the VA. SRP was supported by NIH Predoctoral Grant F30 AA05401.

Keywords

Alcoholism
Blood-brain barrier
Ethanol
Genetics
Preproenkephalin

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S0091-3057(00)00480-9

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@article{1fe9cb6eb4404dda95c1fd939d96e104,

title = "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.",

keywords = "Alcoholism, Blood-brain barrier, Ethanol, Genetics, Preproenkephalin",

author = "Plotkin, {Scott R.} and Banks, {William A.} and Cohn, {Claudia S.} and Kastin, {Abba J.}",

note = "Funding Information: The authors with to thank Melita B. Fasold, Amy Baber, and Gerald Miller for technical assistance; Dr. Charles Ide for supplying the primer sequences for β-actin; Dr. Steven Sabol for supplying the cDNA for PPE; and Dr. John Crabbe for advice. This work was supported by the VA. SRP was supported by NIH Predoctoral Grant F30 AA05401.",

year = "2001",

doi = "10.1016/S0091-3057(00)00480-9",

language = "English (US)",

volume = "68",

pages = "379--387",

journal = "Pharmacology Biochemistry and Behavior",

issn = "0091-3057",

publisher = "Elsevier Inc.",

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TY - JOUR

T1 - Withdrawal from alcohol in withdrawal seizure-prone and -resistant mice

T2 - Evidence for enkephalin resistance

AU - Plotkin, Scott R.

AU - Banks, William A.

AU - Cohn, Claudia S.

AU - Kastin, Abba J.

N1 - Funding Information: The authors with to thank Melita B. Fasold, Amy Baber, and Gerald Miller for technical assistance; Dr. Charles Ide for supplying the primer sequences for β-actin; Dr. Steven Sabol for supplying the cDNA for PPE; and Dr. John Crabbe for advice. This work was supported by the VA. SRP was supported by NIH Predoctoral Grant F30 AA05401.

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

KW - Alcoholism

KW - Blood-brain barrier

KW - Ethanol

KW - Genetics

KW - Preproenkephalin

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U2 - 10.1016/S0091-3057(00)00480-9

DO - 10.1016/S0091-3057(00)00480-9

M3 - Article

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AN - SCOPUS:0034998497

SN - 0091-3057

VL - 68

SP - 379

EP - 387

JO - Pharmacology Biochemistry and Behavior

JF - Pharmacology Biochemistry and Behavior

IS - 3

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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