Rationale Endogenous γ-aminobutyric acid receptor tent decrease in plasma allopregnanolone levels at 8 h WD (GABA R)-active neurosteroids (e.g., allopregnanolone) reg- in all three genotypes, an effect that persisted at 48 h WD ulate central nervous system excitability and many physiolog- only in DBA mice. WSR-1 and WSP-1 mice exhibited ical functions, so fluctuations are implicated in several neuro- unexpected divergent changes in cortical neurosteroids at psychiatric disorders. Pertinently, evidence supports an in- 8 h WD, with the majority of neurosteroids (including verse relationship between endogenous GABA R-active allopregnanolone) being significantly decreased in WSR- neurosteroid levels and behavioral changes in excitability dur- 1 mice, but unaffected or significantly increased in WSP-1 ing ethanol withdrawal (WD). mice. In DBA mice, hippocampal allopregnanolone and Objectives The present studies determined mouse genotype tetrahydrodeoxycorticosterone were significantly de- differences in ten neurosteroid levels in plasma, cortex, and creased at 8 h WD. The pattern of significant correlations hippocampus over the time course of ethanol WD in the WD between allopregnanolone and other GABA R-active Seizure-Prone (WSP) and WD Seizure-Resistant (WSR) se- neurosteroid levels differed between controls and with- lected lines and in the DBA/2J (DBA) inbred strain. drawing mice. Methods Gas chromatography-mass spectrometry was
Psychopharmacology – Springer Journals
Published: Jun 29, 2017
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