Comparative Pharmacokinetics of Ethanol in Inbred Strains of Mice Using Doses Based on Total Body Water

Faulkner, Thomas P.; Cantleberry, Shelly B.; Watts, Val J.; Hussain, Ajaz

doi:10.1111/j.1530-0277.1990.tb00451.x

Cited by 26 publications

(15 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, clearance rates were lower in C57BL/6J mice relative to DBA/2J mice. This finding is compatible with the previous literature, which suggests that C57BL/6J mice have approximately 10-15% slower elimination rates than DBA/2J mice (Faulkner et al, 1990;Grisel et al, 2002). Consistent with the faster elimination rate in DBA/2J mice, estimates for the volume of distribution accounting for body weight and total clearance time were lower in DBA/2J mice relative to C57BL/6J mice.…”

supporting

confidence: 82%

Sex differences in the effect of finasteride on acute ethanol withdrawal severity in C57BL/6J and DBA/2J mice

et al. 2007

View full text Add to dashboard Cite

The neurosteroid allopregnanolone (ALLO) is a potent positive modulator of γ-aminobutyric acid A (GABA A ) receptors that can modulate ethanol (EtOH) withdrawal. The 5α-reductase inhibitor finasteride can block the formation of ALLO and other GABAergic neurosteroids and also reduce certain effects of EtOH. Treatment with finasteride during chronic EtOH exposure decreased EtOH withdrawal severity and blood EtOH concentrations (BECs), suggesting an additional effect of finasteride on EtOH pharmacokinetics. Thus, the purpose of the present study was to determine the effect of finasteride on acute EtOH withdrawal severity, to minimize the effect of finasteride on EtOH metabolism. Male and female C57BL/6J and DBA/2J mice received a pretreatment of finasteride (50 mg/kg i.p.) or vehicle 24 hours prior to an injection of EtOH (4 g/kg i.p.) or saline. Handlinginduced convulsions (HICs) were scored at baseline, and then over a 24 hr period after EtOH or saline injection. In another experiment, plasma estradiol and corticosterone levels were assessed at selected time points (0, 2, 8, and 24 hrs). In a final study, retro-orbital blood samples were collected at 30, 60, 120, and 240 minutes post-EtOH administration to access finasteride's effects on EtOH clearance parameters. Pretreatment with finasteride increased acute EtOH withdrawal severity in female C57BL/6J and DBA/2J mice but decreased withdrawal severity in male mice of both strains. Finasteride did not alter BECs, EtOH clearance, estradiol, or corticosterone concentrations in a manner that appeared to contribute to the sex difference in finasteride's effect on acute EtOH withdrawal severity. These findings suggest that male and female C57BL/6J and DBA/2J mice differ in their sensitivity to changes in ALLO or other GABAergic neurosteroid levels during acute EtOH withdrawal. Sex differences in the modulation of GABAergic 5α-reduced steroids may be an important consideration in understanding and developing therapeutic interventions in alcoholics. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2008 May 25. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe progesterone metabolite allopregnanolone (ALLO; 3α-hydroxy-5α-pregnan-20-one) is a potent positive modulator of γ-aminobutyric acid A (GABA A ) receptors that exerts anxiolytic, sedative, anticonvulsant, and locomotor stimulant effects in animals (Paul and Purdy, 1992;Lambert et al., 1995;Gasior et al., 1999;Rupprecht and Holsboer, 1999;Belelli and Lambert, ...

show abstract

supporting

confidence: 82%

Sex differences in the effect of finasteride on acute ethanol withdrawal severity in C57BL/6J and DBA/2J mice

et al. 2007

View full text Add to dashboard Cite

show abstract

“…There are many differences between mouse strains in their sensitivity to compounds or the ability to metabolize compounds. Mouse strains vary markedly in their sensitivity to ethanol, caffeine, inhalation anesthesia, analgesics, excitotoxin-induced cell death, and mercury and cadmium toxicity (Seale et al ., 1984;Faulkner et al ., 1990;Liu et al ., 1992;Griem et al ., 1997;Sonner et al ., 2000;Habeebu et al ., 2001;Grisel et al ., 2002;Schauwecker, 2003;Wilson et al ., 2003). Furthermore, metabolism is not the only function for which there are strain-specific variations with the potential to influence treatment outcomes.…”

Section: Rodent Models In Related Studiesmentioning

confidence: 99%

Exploiting the rodent model for studies on the pharmacology of lifespan extension

Nadon

2006

Aging Cell

View full text Add to dashboard Cite

SummaryThe rodent is a particularly valuable model with which to test therapeutic interventions for aging, as rodent physiology is close enough to human physiology to give the findings relevance for human aging, and it is small enough to allow for use of statistically robust sample sizes. There are many rodent models to choose from, with advantages and disadvantages to each. The choice of model system, as well as other experimental design decisions such as diet and housing, is extremely important for the success of lifespan studies. These issues are discussed in this review of the use of the rodent model. The National Institute on Aging (NIA) Interventions Testing Program, which has grappled with all of these issues, is described.

show abstract

“…In addition, water content in brain is similar to that in blood (approximately 79 -81%). It is believed that EtOH is mainly distributed to tissues with higher water content (Loeppky et al, 1977;Goldstein, 1983;Faulkner et al, 1990). Thus, ethanol concentrations in brain and blood are expected to be similar when tissue equilibrium is reached.…”

Section: Ethanol Assaysmentioning

confidence: 99%

A Novel Method to Assess Initial Sensitivity and Acute Functional Tolerance to Hypnotic Effects of Ethanol

Ponomarev¹,

Crabbe²

2002

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Loss of righting reflex (LRR) has traditionally been used to estimate hypnotic sensitivity to ethanol in rodents. Traditional methods of monitoring ethanol-induced sedation seems to lack accuracy in estimating blood ethanol concentration (BEC) at initial LRR, a measure of initial sensitivity. Herein, we present a novel method that improves detection of the onset of LRR by using a new apparatus and a loss-of-function criterion of 5 s. DBA/2J and C57BL/6J mice were placed in cylindrical restrainers after injection of 3 g/kg (20% v/v) ethanol. Restrainers were then turned until mice were no longer able to right themselves within 5 s from a position on their back, which represented the endpoint of the initial loss of righting reflex. Initial sensitivity and acute functional tolerance (AFT) to ethanol were assessed in the same group of mice by quantifying BEC at the initial loss and subsequent recoveries of righting reflex over four sequential injections [3 g/kg ϩ (3 ϫ 0.5 g/kg)]. Initial brain sensitivity was calculated from BEC at the first LRR, using the parameters of ethanol uptake kinetics. These values of initial sensitivity were similar for the two strains. On the other hand, DBA/2J mice recovered at higher BEC than C57BL/6J animals. AFT calculated as a difference between the maximum BEC at any recovery and the value of initial sensitivity was greater in DBA/2J mice. These results show that the novel method is a sensitive tool for the measurement of initial sensitivity and detection of AFT to the hypnotic effects of ethanol.

show abstract

Comparative Pharmacokinetics of Ethanol in Inbred Strains of Mice Using Doses Based on Total Body Water

Cited by 26 publications

References 29 publications

Sex differences in the effect of finasteride on acute ethanol withdrawal severity in C57BL/6J and DBA/2J mice

Sex differences in the effect of finasteride on acute ethanol withdrawal severity in C57BL/6J and DBA/2J mice

Exploiting the rodent model for studies on the pharmacology of lifespan extension

A Novel Method to Assess Initial Sensitivity and Acute Functional Tolerance to Hypnotic Effects of Ethanol

Contact Info

Product

Resources

About