TY - JOUR
T1 - Localization of brain 5α-reductase messenger RNA in mice selectively bred for high chronic alcohol withdrawal severity
AU - Roselli, Charles E.
AU - Finn, Timothy J.
AU - Ronnekleiv-Kelly, Sean M.
AU - Tanchuck, Michelle A.
AU - Kaufman, Katherine R.
AU - Finn, Deborah A.
N1 - Funding Information:
This research was supported by USPHS grant AA12439 from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) to DAF. Additionally, this material is the result of work supported with resources and the use of facilities at the Portland VA Medical Center, and DAF was supported in part by funding from the Department of Veterans Affairs . KRK was supported by an F31 predoctoral NRSA ( AA017019 ) from NIAAA. We thank Dr. John Crabbe for graciously supplying the Withdrawal Seizure Prone-1 mice and acknowledge that continued support for the breeding colony has been provided by a grant from the Department of Veterans Affairs to Dr. Crabbe. We thank the Portland Alcohol Dependence Core (funded by AA10760 to Dr. Crabbe) for their assistance with the induction of physical dependence and thank Mr. Chris Snelling for the analysis of blood ethanol concentrations.
PY - 2011/12
Y1 - 2011/12
N2 - Several lines of evidence suggest that fluctuations in endogenous levels of the γ-aminobutyric acid (GABA)ergic neurosteroid allopregnanolone (ALLO) represent one mechanism for regulation of GABAergic inhibitory tone in the brain, with an ultimate impact on behavior. Consistent with this idea, there was an inverse relationship between ALLO levels and symptoms of anxiety and depression in humans and convulsive activity in rodents during alcohol withdrawal. Our recent studies examined the activity and expression of 5α-reductase (Srd5a1), the rate-limiting enzyme in the biosynthesis of ALLO, during alcohol withdrawal in mice selectively bred for high chronic alcohol withdrawal (Withdrawal Seizure-Prone [WSP]) and found that Srd5a1 was downregulated in the cortex and hippocampus over the time course of dependence and withdrawal. The purpose of the present studies was to extend these findings and more discretely map the regions of Srd5a1 expression in mouse brain using radioactive in situ hybridization in WSP mice that were ethanol naïve, following exposure to 72. h ethanol vapor (dependent) or during peak withdrawal. In naïve animals, expression of Srd5a1 was widely distributed throughout the mouse brain, with highest expression in specific regions of the cerebral cortex, hippocampus, thalamus, hypothalamus, and amygdala. In dependent animals and during withdrawal, there was no change in Srd5a1 expression in cortex or hippocampus, which differed from our recent findings in dissected tissues. These results suggest that local Srd5a1 mRNA expression in WSP brain may not change in parallel with local ALLO content or withdrawal severity.
AB - Several lines of evidence suggest that fluctuations in endogenous levels of the γ-aminobutyric acid (GABA)ergic neurosteroid allopregnanolone (ALLO) represent one mechanism for regulation of GABAergic inhibitory tone in the brain, with an ultimate impact on behavior. Consistent with this idea, there was an inverse relationship between ALLO levels and symptoms of anxiety and depression in humans and convulsive activity in rodents during alcohol withdrawal. Our recent studies examined the activity and expression of 5α-reductase (Srd5a1), the rate-limiting enzyme in the biosynthesis of ALLO, during alcohol withdrawal in mice selectively bred for high chronic alcohol withdrawal (Withdrawal Seizure-Prone [WSP]) and found that Srd5a1 was downregulated in the cortex and hippocampus over the time course of dependence and withdrawal. The purpose of the present studies was to extend these findings and more discretely map the regions of Srd5a1 expression in mouse brain using radioactive in situ hybridization in WSP mice that were ethanol naïve, following exposure to 72. h ethanol vapor (dependent) or during peak withdrawal. In naïve animals, expression of Srd5a1 was widely distributed throughout the mouse brain, with highest expression in specific regions of the cerebral cortex, hippocampus, thalamus, hypothalamus, and amygdala. In dependent animals and during withdrawal, there was no change in Srd5a1 expression in cortex or hippocampus, which differed from our recent findings in dissected tissues. These results suggest that local Srd5a1 mRNA expression in WSP brain may not change in parallel with local ALLO content or withdrawal severity.
KW - Convulsion
KW - Ethanol
KW - GABA
KW - In situ hybridization
KW - Neurosteroid
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U2 - 10.1016/j.alcohol.2011.08.002
DO - 10.1016/j.alcohol.2011.08.002
M3 - Article
C2 - 21917407
AN - SCOPUS:81055156906
SN - 0741-8329
VL - 45
SP - 763
EP - 772
JO - Alcohol
JF - Alcohol
IS - 8
ER -