Inhibition of 5α‐Reduced Steroid Biosynthesis Impedes Acquisition of Ethanol Drinking in Male C57BL/6J Mice

Ford, Matthew M.; Yoneyama, Naomi; Strong, Moriah N.; Fretwell, Andrea M.; Tanchuck, Michelle A.; Finn, Deborah A.

doi:10.1111/j.1530-0277.2008.00718.x

Cited by 42 publications

(56 citation statements)

References 22 publications

(45 reference statements)

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“…85 Mr Q currently takes finasteride and zolpidem. Finasteride reduces alcohol intake in mice 86 but is unlikely to interact meaningfully with alcohol. Zolpidem and alcohol produce additive levels of sedation that could interfere with activities occurring after the time of dosing and could produce excessive morning sedation, but risk is unlikely if zolpidem dosing occurs just before bed and 1 or 2 drinks are taken with dinner.…”

Section: Endogenous Sex Steroid Hormonesmentioning

confidence: 99%

A 42-Year-Old Man Considering Whether to Drink Alcohol for His Health

Mukamal

2010

JAMA

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Alcohol consumption is widespread and, in excess, a leading cause of morbidity and mortality worldwide. At the same time, a consistent body of observational evidence has found that individuals who consume alcohol within recommended limits have a lower risk of coronary heart disease than do abstainers. These observations have led many to consider small amounts of alcohol as a cardioprotective strategy. Mr Q, a 42-year-old man who has consistently sought ways to preserve his health, is at a crossroads in his discussions with his physicians about the health effects of his regular, limited alcohol intake. The discussion reviews the epidemiology of drinking in the United States, the established effects of moderate alcohol intake on key pathophysiological biomarkers and pathways, the strengths and limitations of observational evidence linking alcohol intake to lower risk of coronary heart disease, other chronic diseases linked to moderate alcohol intake, and a framework in which Mr Q can discuss the potential risks and benefits of alcohol consumption with his physicians.

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Section: Endogenous Sex Steroid Hormonesmentioning

confidence: 99%

A 42-Year-Old Man Considering Whether to Drink Alcohol for His Health

Mukamal

2010

JAMA

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“…Indeed, to our knowledge, the effects of finasteride have so far generally been explored after the administration of very high doses [2,8,9,10,11,12,13,14,15,16,17,18]. We demonstrated that, in agreement with the well-known effect of finasteride in the prostate [35], a significant decrease in its relative weight was observed at the end of the subchronic treatment with the drug.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the metabolites of PROG and T are involved in the regulation of neuroendocrine events, behavior, affection, learning and memory, synaptic and glial plasticity and adult hippocampal neurogenesis as well as in the response of brain tissue to injury and neurodegeneration (i.e., regulating neuronal survival, axonal regeneration and gliosis) [1,5,6,7]. Finasteride has been used as a tool to evaluate whether the effects of PROG or T in the nervous tissue could be ascribed to their conversion into 5α-reduced metabolites [2,8,9,10,11,12,13,14,15,16,17,18]. However, despite of the wide therapeutic use of this inhibitor (e.g., human benign prostatic hyperplasia and androgenic alopecia), the effects of finasteride per se in the nervous system have been poorly explored.…”

Section: Introductionmentioning

confidence: 99%

“…However, despite of the wide therapeutic use of this inhibitor (e.g., human benign prostatic hyperplasia and androgenic alopecia), the effects of finasteride per se in the nervous system have been poorly explored. The effects of short exposures (i.e., a few days) to high doses (i.e., 50 mg/kg) of finasteride have been assessed in experimental models [2,8,9,10,11,12,13,14,15,16,17,18]. However, the effects of subchronic treatments with finasteride at low doses, more similar to those used in clinical practice, and the consequences of its withdrawal have yet to be clarified.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Subchronic Finasteride Treatment and Withdrawal on Neuroactive Steroid Levels and Their Receptors in the Male Rat Brain

et al. 2015

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The enzymatic conversion of progesterone and testosterone by the enzyme 5alpha-reductase exerts a crucial role in the control of nervous function. The effects of finasteride in the brain, an inhibitor of this enzyme used for the treatment of human benign prostatic hyperplasia and androgenic alopecia, have been poorly explored. Therefore, the effects of a subchronic treatment with finasteride at low doses (3 mg/kg/day) and the consequences of its withdrawal on neuroactive steroid levels in plasma, cerebrospinal fluid and some brain regions as well as on the expression of classical and non-classical steroid receptors have been evaluated in male rats. After subchronic treatment (i.e., for 20 days) the following effects were detected: (i) depending on the compartment considered, alteration in the levels of neuroactive steroids, not only in 5alpha-reduced metabolites but also in its precursors and in neuroactive steroids from other steroidogenic pathways and (ii) an upregulation of the androgen receptor in the cerebral cortex and beta3 subunit of the GABA-A receptor in the cerebellum. One month after the last treatment (i.e., withdrawal period), some of these effects persisted (i.e., the upregulation of the androgen receptor in the cerebral cortex, an increase of dihydroprogesterone in the cerebellum, a decrease of dihydrotestosterone in plasma). Moreover, other changes in neuroactive steroid levels, steroid receptors (i.e., an upregulation of the estrogen receptor alpha and a downregulation of the estrogen receptor beta in the cerebral cortex) and GABA-A receptor subunits (i.e., a decrease of alpha 4 and beta 3 mRNA levels in the cerebral cortex) were detected. These findings suggest that finasteride treatment may have broad consequences for brain function.

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“…Moreover, others and we have shown that restricted access to ethanol for 2-4 h/day in a two-bottle setup, where mice have the choice between water and ethanol, results in high preference for ethanol [20,21]. Although preference for the ethanol solution often does not exceed 50% for C57BL/6J mice in a 24-h two-bottle choice paradigm [4,6], in the limited access paradigm C57Bl/6J mice drink more than 2 g/kg ethanol in 2-4 h sessions with a preference exceeding 80% [20,21].…”

Section: Introductionmentioning

confidence: 95%

A grandparent-influenced locus for alcohol preference on mouse chromosome 2

Lesscher

Kas

Elst³

et al. 2009

Pharmacogenetics and Genomics

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Using a limited access choice paradigm, we found that mouse chromosome 2 carries an allelic variant of a locus for ethanol intake and a distinct locus selective for ethanol preference. The heritability of alcoholism has been suggested to be parent-specific, perhaps resulting from genetic imprinting. Our findings suggest that grandparent-influenced vulnerability for ethanol consumption is conferred by genes on chromosome 2, providing important new leads to enhance our understanding of the heritability of alcoholism.

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Inhibition of 5α‐Reduced Steroid Biosynthesis Impedes Acquisition of Ethanol Drinking in Male C57BL/6J Mice

Cited by 42 publications

References 22 publications

A 42-Year-Old Man Considering Whether to Drink Alcohol for His Health

A 42-Year-Old Man Considering Whether to Drink Alcohol for His Health

Effects of Subchronic Finasteride Treatment and Withdrawal on Neuroactive Steroid Levels and Their Receptors in the Male Rat Brain

A grandparent-influenced locus for alcohol preference on mouse chromosome 2

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