Fat rats and cocaine

Every so often, Sci comes across a study that at first looks incredibly exciting...and then kind of becomes a bit of a let down. Not because it was a BAD study, mind, but because I want MORE. Thus was this study.

So let's talk about high fat diets, and let's talk about coke. But mostly coke.

ResearchBlogging.org Wellman, et al. "Impairment of acquisition of cocaine self-administration in rats maintained on a high-fat diet" Pharmacology, Biochemistry, and Behavior, 2007.

First off, cocaine self-administration. In drug abuse studies, cocaine self-administration is the gold standard for how we study cocaine abuse. Give a rat a lever in a cage, and a catheter in its back. The catheter is connected to a syringe which is filled with a dilute cocaine solution. When the rat presses the lever (often at a specific time or in a specific pattern), the animal gets a shot of cocaine in the catheter and straight into the vein.

The great thing about this method (though the way it is executed ends up having some drawbacks, but I'm not going to go into those right now) is that the drug doing is ALL up to the rat, and thus it's a lot more similar to what drug taking is like in the human condition. This also means that you can use variations in rat self-administration to suggest how much the rat "wants" the drug. Which is what they'll be doing here.

Now, on to diets. We know that diets will influence the way rats do coke. For example, if you leave a rat hungry, it will do more coke. But there's more detail than that. Rats LOVE fat. If you feed a rat Crisco (really), it will eat until it's a little ball of rat with a bellyache. Fat is obviously really rewarding to rats. Not only that, it's a natural reward. Many people think that drugs of abuse work by hijacking the natural reward system. So people have thought that if you eat a lot of high fat, you might do more coke, with the two kinds of reward applying to each other. So this might mean, if you give a rat a lot of fat, it might administer LESS cocaine, as the fat would substitute one reward (cocaine) for another (fat).

That was the assumption that these authors were looking at. So they gave half of their rats a high fat diet, and the other half a normal diet. They then looked at both groups and how they ACQUIRED cocaine self-administration. Because rats don't just walk into a cage and start banging on a coke lever, mind. They have to be trained to do it, and acquire cocaine self-administration at a certain rate. Not only that, some rats will never acquire cocaine self-administration AT ALL. They were hoping that differences in cocaine self-administration acquisition would reflect reduced reinforcing properties of cocaine in high fat rats, by substituting the fat for the cocaine.

The hypothesis was that rats on a high fat diet might end up acquiring cocaine self-administration at lower rates than rats on a normal diet. Above you can see the acquisition rates in the percent of rats that acquired the cocaine self-administration. The dark circles are the normal rats and the open circles are the high fat rats. You can see that the normal rats acquired self-administration at greater rates than the high fat rats did, which the authors state as an alteration in the reinforcing properties of the cocaine in the rats fed the high fat diet.

Unfortunately, the paper stops there, it's a small little chunk of data, and leaves far more questions than it answers (though I bet they are working on the questions and probably will publish them soon). For one thing, their numbers are pretty low. They got 42% acquiring cocaine self-administration in the normal rats, and 25% acquiring cocaine self-administration in the high fat rats by the end of the experiment. BUT. That's out of a total of 7-8 rats EACH. This means 3 our of 7 acquired for normal animals, and 2 our of 8 for the high fat. That's some pretty small numbers, but not totally unexpected. Part of the issues here could be the dose. They used 0.2 mg/kg cocaine per cocaine infusion, which is pretty low, and might be why they got low rates of acquisition in their animals. Other studies have shown that higher doses like 0.5 or 1.0 mg/kg cocaine per infusion produce higher rates of acquisition, like this:


(That's gonna fill your browser window, ain't it..., from Kosten, et al, 1997).

So I wonder if they had used a range of doses (called a dose-response curve) if they would have seen the same thing, or if, at higher doses, the high fat rats would administer cocaine just like the rats on normal diets.

Not only that, there's the question of what acquisition of cocaine self-administration really MEANS in these rats. The authors think that it may mean that cocaine is less reinforcing in these animals (and they may be right), but there are lots of other tests that I think could be performed to be sure. The dose response curve I mentioned above is probably a good one. There is also the question of whether cocaine is less REWARDING in these animals (reward vs reinforcement is a very big distinction is drug abuse neuropharmacology, and basically breaks down to whether it feels good and you want it OR it makes you bang on the lever again, which is something the drug may do regardless of whether it feels good. It's complicated, but neuropharmacologists will get very uptight if you use "reward" where you should use ''reinforce".) This is a question that could be answered by these researchers using a progressive ratio schedule, where a rat bangs on the lever once, gets coke. But the SECOND one is going to be harder to get, that requires two presses. Then four. Then 8, then 16...you get the idea. The amount that the rat is willing to spend working for the cocaine is thought to be a measure of its rewarding effects in the rat, and it would be interesting to see whether the rats fed a high fat diet find cocaine less or more rewarding.

So what does this paper tell us? It tells us that maybe animals fed a high fat diet will not develop cocaine self-administration as quickly as animals fed a low fat diet, and plays into the question of how DIET can affect how HUMANS respond to drugs. Thus, while a starving starlet may find cocaine more reinforcing, someone on a higher fat diet may not. And eventually, when these interactions between diet and drugs are better known, it may be possible to use this information to help people being treated for drug abuse.

References:

WELLMAN, P., NATION, J., & DAVIS, K. (2007). Impairment of acquisition of cocaine self-administration in rats maintained on a high-fat diet Pharmacology Biochemistry and Behavior, 88 (1), 89-93 DOI: 10.1016/j.pbb.2007.07.008

Kosten TA, Miserendino MJ, Haile CN, DeCaprio JL, Jatlow PI, & Nestler EJ (1997). Acquisition and maintenance of intravenous cocaine self-administration in Lewis and Fischer inbred rat strains. Brain research, 778 (2), 418-29 PMID: 9459563

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