We're trying to develop a more humane protocol for perfusion in laboratory mice. We had mice waking up during perfusion from anesthesia with avertin, but not with pentobarbital anesthesia using buprenorphine (for pain control) as a pre-med. Currently there is a shortage/backorder of pentobarbital so we are seeking alternative. We are considering a combination of ketamine and xylazine for anesthesia with buprenorphine + Acepromazine OR Midazolam pre-med.

We like this option because of its welfare benefits: 1) it can be given sub-Q, avoiding painful/uncomfortable IP, and 2) it provides excellent pain control.

But we are also concerned about potential effects of the drug combination (especially ketamine) on our outcome measures - primarily markers of neuronal activity and plasticity (e.g. IEGs, dendritic spine density, BDNF etc. though we are not sure precisely which assays we will be running yet).

  • Is the use of ketamine as an anesthetic before brain collection accepted in broader neuroscientific community? Or specifically behavioural neuroscientists working with laboratory rodents? Or is it a hard no-go for various reasons (e.g. having affinity for many membrane-bound proteins potentially causing many unknown alterations in the post-mortem brain)?
  • Are there dose dependent effects of ketamine (+/- xylazine) on readouts? For instance, we could reduce the dose of ketamine/xylazine by adding acepromazine to the induction protocol (leave ace out of the pre-med, and use ket/xyl/ace combo SQ to induce anesthesia), if a smaller dose of ket/xyl = less likely to impact outcomes.
  • Do you have any other recommendations for anesthetics that can be administered sub-Q or IM (avoiding IP for welfare considerations)?
  • Are there studies on rodents using ketamine + xylazine prior to perfusion and examining markers of neuronal activity and plasticity (please provide reference)? And/or are you (the reader) currently using this drug combination with mice or rats to do neuroscience? Or know anyone who is?
  • Are there any studies examining the post-mortem effects of ketamine + xylazine on a variety of neuroscientific assays versus other anesthetic agents (please provide reference)?
  • Thank you all very much for your help!

    More Lindsey Kitchenham's questions See All
    Similar questions and discussions