I'm planning a study in which moderate doses of diazepam would be given to rats each day for several months. However at the end of this, I would like to test their behaviour without the acute effects of the drug, and without them experiencing withdrawal. How gradually would I need to taper the dose to avoid the rats experiencing withdrawal?
If humans are any guide, there will be much variation - as with heroin and alcohol. If you want to speed up withdrawal without producing rodent status epilepticus, low-dose flumazenil infusions enable humans to withdraw from fistfuls of diazepam (e.g. 500mg/day) in a week without fits and I think it works for rats as well.
Thanks Colin - I'm trying to have the animals drug free within a month, after approx six months with a daily dose. All I could find was a study suggesting that anxiety was still slightly elevated two weeks after discontinuing a daily dose regimen (File SE. Hum Psychopharmacol. 1989;4:59–63). Given the lack of other literature out there, I'm going to try tapering it 5% per day for three weeks and see how I go - it'll require monitoring of course.
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