Conditioned Place Aversion (CPA) assays in Mice.. Thoughts?

So I want to assay the aversive effect of an intervention on mice, and I’m thinking that a CPA assay may be the way to go. Much of the operant conditioning assay work I’ve seen is done in rats, but some papers are coming out using mice. I’ve listed some below.

If you’ve used CPA before in mice, and you’d be willing to share your in-house protocol or any tips, I’d very much appreciate it. @ram_kandasamy and @LegakisL: do you guys have any experience with mice using CPA?

References for CPA assay in mice

Sorry only rats, but it would be cool to show a dose-effect curve for CFA in a CPA assay. As a proof of principle that could be done, a group has done CPA with KOR agonists in mice. KOR agonists are not considered pain states but they demonstrate similar endpoints in the measures we look at with behavior (causes ICSS depression and (I believe) depression of nesting).

I’ve only used rats as well, unfortunately.

I was going to suggest something similar to what Luke said. Rather than performing a CPA experiment that will likely need multiple conditioning days (depending on how aversive the drug is), can you look at depression of a normally rewarding activity as a measure of aversiveness? This doesn’t need to be ICSS, but it can be something as simple as sucrose preference (i.e., does the intervention cause an animal to drink less sugar water?). This is likely a measure of ‘anhedonia’, but I think you could argue that anhedonia is aversive.

@ram_kandasamy That’s an interesting point. So what do mice like to do? They like to tear up cotton (nesting), run around, burrow. Sucrose preference sounds interesting. I may need to set that up. I’ll keep you posted.

Ethologically relevant behaviors like burrowing and nesting may be a good start because it’s relatively easy. That is, you won’t need much work or equipment to get an assay up and running. You’ll need additional equipment to do ICSS, wheel running, or locomotion if you guys don’t have something like that set up already.

Good luck, let us know how it goes.

We’ve had a helluva time trying to get CPA and burrowing to work in mice. We tried CPA to formalin way back in the day, and got nothing. For burrowing, mice definitely are as eager to do it as rats, but neither SNI nor CFA seem to reduce it, in either CD-1 or C57BL/6 mice.

@jmogil Hmm. Good to know. It’s amazing that some of these quite noxious stimuli don’t affect certain behaviors in rodents. If the mice don’t do less of what they like to do, how much pain are they really in?