Psychopharmacology

, Volume 231, Issue 17, pp 3401–3414

Quantification of ten neuroactive steroids in plasma in Withdrawal Seizure-Prone and -Resistant mice during chronic ethanol withdrawal

  • Christopher Snelling
  • Michelle A. Tanchuck-Nipper
  • Matthew M. Ford
  • Jeremiah P. Jensen
  • Debra K. Cozzoli
  • Marcia J. Ramaker
  • Melinda Helms
  • John C. Crabbe
  • David J. Rossi
  • Deborah A. Finn
Original Investigation

DOI: 10.1007/s00213-014-3618-y

Cite this article as:
Snelling, C., Tanchuck-Nipper, M.A., Ford, M.M. et al. Psychopharmacology (2014) 231: 3401. doi:10.1007/s00213-014-3618-y

Abstract

Rationale

The rapid membrane actions of neuroactive steroids, particularly via an enhancement of γ-aminobutyric acidA receptors (GABAARs), participate in the regulation of central nervous system excitability. Prior evidence suggests an inverse relationship between endogenous GABAergic neuroactive steroid levels and behavioral changes in excitability during ethanol withdrawal.

Objectives

Previously, we found that ethanol withdrawal significantly decreased plasma allopregnanolone (ALLO) levels, a potent GABAergic neuroactive steroid, and decreased GABAAR sensitivity to ALLO in Withdrawal Seizure-Prone (WSP) but not in Withdrawal Seizure-Resistant (WSR) mice. However, the effect of ethanol withdrawal on levels of other endogenous GABAAR-active steroids is not known.

Methods

After validation of a gas chromatography-mass spectrometry method for the simultaneous quantification of ten neuroactive steroids, we analyzed plasma from control male WSP-1 and WSR-1 mice and during ethanol withdrawal.

Results

We quantified levels of nine neuroactive steroids in WSP-1 and WSR-1 plasma; levels of pregnanolone were not detectable. Basal levels of five neuroactive steroids were higher in WSR-1 versus WSP-1 mice. Ethanol withdrawal significantly suppressed five neuroactive steroids in WSP-1 and WSR-1 mice, including ALLO.

Conclusions

Due to lower basal levels of some GABAAR-active steroids in WSP-1 mice, a withdrawal-induced decrease in WSP-1 mice may have a greater physiological consequence than a similar decrease in WSR-1 mice. Because WSP-1 mice also exhibit a reduction in GABAAR sensitivity to neuroactive steroids during withdrawal, it is possible that the combined decrease in neuroactive steroids and GABAAR sensitivity during ethanol withdrawal in WSP-1 mice represents a neurochemical substrate for severe ethanol withdrawal.

Keywords

Allopregnanolone Androstanediol Tetrahydrodeoxycorticosterone Alcohol Gas chromatography Mass spectrometry DHEA Pregnenolone Male 

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Christopher Snelling
    • 1
  • Michelle A. Tanchuck-Nipper
    • 1
  • Matthew M. Ford
    • 1
    • 2
  • Jeremiah P. Jensen
    • 1
  • Debra K. Cozzoli
    • 1
  • Marcia J. Ramaker
    • 1
  • Melinda Helms
    • 1
  • John C. Crabbe
    • 1
    • 3
  • David J. Rossi
    • 1
    • 4
  • Deborah A. Finn
    • 1
    • 3
  1. 1.Department of Behavioral NeuroscienceOregon Health and Science UniversityPortlandUSA
  2. 2.Division of Neuroscience, Oregon National Primate Research CenterOregon Health and Science UniversityBeavertonUSA
  3. 3.Department of Veterans Affairs Medical CenterPortland Alcohol Research CenterPortlandUSA
  4. 4.Department of Integrative Physiology and NeuroscienceWashington State UniversityPullmanUSA

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