I am going to treat transgenic mice for 2 months (s.c. on alternate days). I am interested in studying the effects of treatment in several behavioral test such as open field test, novel objection recognition, tail suspension, forced swimming stress, sucrose preference tests and Morris water maze tests.
I think it depends what you are treating them with - typically, behavioural tests such as you describe can take place within minutes of dosing.
Are you specifically looking at the long-term changes caused by a drug when it is no longer in the system? Also, bear in mind that some test (e.g. sucrose preference) require training, which may be affected by drug treatment also (e.g. learning/cognitive functions)
I have performed a similar set-up, with treatment for 1, 3, and 5 months. After end of treatment I had a 4 week wash-out period. This because I did not want to study the direct effects of the treatment but rather the long-term effects caused by the treatment, However, a problem was that I could not know for sure if the wash-out period then was responsible for the effects due to e.g. withdrawal effects of the substance. Depending on what your scientific question is, the best could be to do both. See effects directly after end of treatment (or AT the end of treatment) and after a wash-out period. That is what I would like to do.
References: Van Dam D, De Deyn PP. Drug discovery in dementia: the role of rodent models. Nature Reviews Drug Discovery 2006;5(11):956-70. Bengtsson SK, Johansson M, Bäckström T, Wang M. Chronic Allopregnanolone Treatment Accelerates Alzheimer's Disease Development in AβPPSwePSEN1ΔE9 Mice. Journal of Alzheimer's Disease. 2012;31(1):71-84.
What are you trying to model, what is the human condition? If your question had a bit more detail i think you could get better answers. I would have a washout period relevant to what i am trying to model. In addition, you will want to find out the half-life of the drugs you use in mice (probably different from human half-life) as this may be important to measuring acute versus chronic effects. Also, as soon as you stop a drug treatment there will be changes in proteins e.g. receptor up- or down-regulation - it will be very complicated and the changes will likely take place of days or weeks.
Thank you for your comments. I am using triple transgenic mouse model of AD. The compound has half like of 12 hours. The treatment should decrease beta amyloid plaques deposition. My aim is to see long term effects of treatment on cognitive and non cognitive behavior of AD mice.
if you are only measuring behavior then you could test them at multiple times after withdrawal, this would provide better information than just testing on one day. for example day 1, 3, 7, 14 and 28
Hi Gaurav,
As your test compound half life is 12 hours and I don't think that you have to go wash period to check the changes in the behaviour. Your main aim is to check the effect of test compound on behaviour and/or memory and/or betaamyloid levels, I suggest you to test periodically like Day 1, 3, 7, 14, 21, 28, 42 60 day during treatment and day 1, 7, 14 and 30 day of withdrawal. So you can better correlate with varies parameters like drug levels, chronic treatment, betaamyloid levels and changes in behaviour (PKPD).
Try to get as much as information as this is a transgenic mouse model.
All the best.
Regards
Ramanatha
Interesting thread ! Also, what is the minimum washout period between assessing sucrose preference over 48h multiple times overtime ?
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