Local Changes in Neurosteroid Levels in the Substantia Nigra Reticulata and the Ventral Tegmental Area Alter Chronic Ethanol Withdrawal Severity in Male Withdrawal Seizure-Prone Mice

December 2012 in “ Alcoholism Clinical and Experimental Research ”

Michelle A. Tanchuck, Debra K. Cozzoli, Ingrid He, Katherine R. Kaufman, Christopher Snelling, John C. Crabbe, Gregory P. Mark, Deborah A. Finn

allopregnanolone finasteride GABA A receptors GABAergic neurosteroids ALLO FIN Propecia

Studysummary This study found that in Withdrawal Seizure-Prone mice, ethanol withdrawal decreased the sensitivity of GABA A receptors to GABAergic neurosteroids in certain areas of the brain.

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The study investigated the effects of neurosteroid manipulations in the substantia nigra reticulata (SNR) and ventral tegmental area (VTA) on ethanol (EtOH) withdrawal in male Withdrawal Seizure-Prone mice (WSP-1). Researchers found that allopregnanolone (ALLO) infusion had a strong anticonvulsant effect in EtOH-naïve mice but showed reduced efficacy during EtOH withdrawal. Conversely, finasteride (FIN) administration into the SNR delayed proconvulsant effects in EtOH-naïve mice, while infusion into the VTA prolonged EtOH withdrawal. The study concluded that EtOH withdrawal decreased the sensitivity of GABAARs to GABAergic neurosteroids in these brain regions, indicating a behavioral tolerance to ALLO's anticonvulsant effects during withdrawal.

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Research cited in this study

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research The Neurosteroid Environment in the Hippocampus Exerts Bi-Directional Effects on Seizure Susceptibility in Mice

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research Sex Differences in the Effect of Finasteride on Acute Ethanol Withdrawal Severity in C57BL/6J and DBA/2J Mice

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In this study, finasteride altered acute ethanol withdrawal severity differently in male and female mice, highlighting sex differences in sensitivity to changes in neurosteroid levels.

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research Attenuating 5α-Pregnane-3α-Ol-20-One Formation in the Hippocampus of Female Rats Increases Pentylenetetrazole-Induced Seizures

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research The Role of Pregnane Neurosteroids in Ethanol Withdrawal: Behavioral Genetic Approaches

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research Finasteride, a 5alpha-Reductase Inhibitor, Blocks the Anticonvulsant Activity of Progesterone in Mice

48 citations , February 1999 in “PubMed”

This study found that the anticonvulsant effects of progesterone against PTZ-induced seizures in mice require conversion to allopregnanolone, as shown by the reversal of these effects with a 5alpha-reductase inhibitor.