Long-lasting anticonvulsant effects of diazepam in different mouse strains: Correlations with brain concentrations and receptor occupancy

File, Sandra E.; Greenblatt, David J.; Martin, Ian L.; Brown, ChloëL.

doi:10.1007/bf00431698

Cited by 28 publications

(8 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In spite of these differences in receptor occupancies, the seizure thresholds for the NIH strain did not differ significantly from those for the C3H/HE strain and, if anything, they tended to be lower. These results are in agreement with previous experiments (File et al 1985) in which the two strains were compared 6 h after a single dose of diazepam.…”

Section: Discussionsupporting

confidence: 94%

“…In the earlier study (File et al 1985), a receptor occupancy of approximately 50% with diazepam was required to protect 100% of mice against the seizures induced by an 80 mg/kg IP dose of pentylenetetrazol. In this study an occupancy of some 80-100% was required to produce the same level of protection with oxazepam.…”

Section: Discussionmentioning

confidence: 98%

“…Strain differences have been observed in the picrotoxin seizure threshold in mice (Burt 1962) and recent evidence has also revealed the existence of strain differences in benzodiazepine receptor binding in rats (Shephard et al 1982). A paper by File et al (1985) compared the anticonvulsant potency of a single dose of diazepam against pentylenetetrazol-induced seizures with in vivo receptor occupancy for four strains of mice. The strains differed markedly in the rate at which the anticonvulsant action of diazepam was lost and there was no correlation between these differences and strain differences in vivo receptor occupancy.…”

mentioning

confidence: 97%

See 2 more Smart Citations

Evidence of strain differences in GABA-benzodiazepine coupling

Wilks

File

Martin³

1987

Psychopharmacology

Self Cite

View full text Add to dashboard Cite

The effects of a single dose of oxazepam on seizure threshold, receptor occupancy and brain oxazepam concentration were investigated at several time points after drug treatment in two inbred strains of mice (NIH and C3H/HE). The C3H/HE strain showed a greater sensitivity to the effects of both pentylenetetrazol and oxazepam. Furthermore, the C3H/HE strain showed decreases in both receptor occupancy and seizure threshold across time, whereas the NIH strain showed no change in either measure. Although within-strain correlations were observed between seizure threshold and receptor occupancy, the C3H/HE strain had similar seizure thresholds to the NIH strain throughout but lower percentage receptor occupancies, thus a between-strain correlation was not observed. The C3H/HE strain had a higher number of specific benzodiazepine binding sits and these results may reflect a strain difference in GABA-benzodiazepine receptor coupling. In a further experiment, the development of acute tolerance to the effects of oxazepam was investigated. Brain concentrations of oxazepam and receptor occupancies were determined for each strain of mouse, at two different time points (1.5 and 7.5 h after drug treatment), at which equivalent seizure thresholds were obtained by manipulating the starting dose of oxazepam. For each strain, when equivalent seizure thresholds were observed at different time points, equivalent receptor occupancies were also observed. However, a trend towards higher brain concentrations of oxazepam at the later time point was detected for the two strains, suggesting that there may be some decrease across time in the affinity of the receptor for oxazepam.

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 97%

See 1 more Smart Citation

Evidence of strain differences in GABA-benzodiazepine coupling

Wilks

File

Martin³

1987

Psychopharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Mouse strain differences have also been reported with regard to the anti-seizure effects of a wide variety of drugs, including benzodiazepines [89,90], phenobarbital [91], valproic acid [91], delta-aminolevulenic acid [92], MK-801 [93], levetiracetam [94], phenytoin [94], and neurosteroids [95]. These studies utilized diverse paradigms to induce acute seizures, but all documented significant effects of genetic background on measured responses.…”

Section: Interstrain Differences In the Expression Of Seizures Andmentioning

confidence: 99%

The relevance of inter- and intrastrain differences in mice and rats and their implications for models of seizures and epilepsy

Löscher¹,

Ferland

Ferraro

2017

Epilepsy & Behavior

View full text Add to dashboard Cite

It is becoming increasingly clear that the genetic background of mice and rats, even in inbred strains, can have a profound influence on measures of seizure susceptibility and epilepsy. These differences can be capitalized upon through genetic mapping studies to reveal genes important for seizures and epilepsy. However, strain background and particularly mixed genetic backgrounds of transgenic animals need careful consideration in both the selection of strains and in the interpretation of results and conclusions. For instance, mice with targeted deletions of genes involved in epilepsy can have profoundly disparate phenotypes depending on the background strain. In this review, we discuss findings related to how this genetic heterogeneity has and can be utilized in the epilepsy field to reveal novel insights into seizures and epilepsy. Moreover, we discuss how caution is needed in regards to rodent strain or even animal vendor choice, and how this can significantly influence seizure and epilepsy parameters in unexpected ways. This is particularly critical in decisions regarding the strain of choice used in generating mice with targeted deletions of genes. Finally, we discuss the role of environment (at vendor and/or laboratory) and epigenetic factors for inter- and intrastrain differences and how such differences can affect the expression of seizures and the animals’ performance in behavioral tests that often accompany acute and chronic seizure testing.

show abstract

“…The results of a number of studies suggest that genetic variables affect behavioral responses to benzodiazepines (File et al 1985;Crabbe et al 1986;Seredenin et al 1986;Gallaher et al 1987). Most of these have focused on responses to benzodiazepine receptor agonists.…”

mentioning

confidence: 99%