Sci is SO happy that friend of the blog Daniel Oppenheimer (who writes for the College of Natural Sciences at UT Austin, good going UT Austin!) passed me along a copy of this paper! It’s a paper I’ve been wanting a good look at for ages, one which almost every behavioral pharmacologist learns about, but no one can EVER remember it by name or remember exactly how it worked. Most people who I’ve talked to refer to it as “that paper with the rat playground”. Yeah, basically that’s it.
And now I finally HAVE the paper! I was hoping in my little heart that there might actually be a picture of the happy rat playground, maybe a big thing with lots of wood shavings and colored blocks and tunnels and happy rats.
(Source)
Sadly, it was not to be, no photos, and the playground doesn’t sound as great as I imagined. But that’s not important to ME, it’s important to the RATS, and it’s particularly important to how it impacts the way rats take DRUGS.
Hadaway, et al. “The Effect of Housing and Gender on Preference for Morphine-Sucrose Solutions in Rats” Psychopharmacology, 1979.
That humans can get rats to self-administer drugs in various forms has been known and studied for a long time, and has impacted how we work with humans who are addicted to drugs, and what we know about the mechanisms of drug abuse.
Scientists have wondered whether the self-administration of drugs in a fundamental vulnerability in rats. Sci would say it’s not a fundamental vulnerability in RATS, it’s a fundamental vulnerability in MANY animals, including humans, under certain conditions. And then the question becomes: what are those conditions? WHY are the rats self-administering drugs?
The scientists in this paper hypothesized that part of the high drug self-administration (in this case, choosing a sipper with morphine over one with just water) was due to, well, bored and lonely rats. In order to control and measure how much drug a given rat is taking over time, it is often essential to single house the rats (not all drugs are like this, but some are, and I’ll get that more later). The authors hypothesized that rats that were lonely and bored would take more drugs than rats that weren’t.
And so they built a rat colony! The methods describe it as being a big enclosure (8 meters wide and tall) filled with wood shavings and metal normal rat cages for rats to hide and play in. Half of the rats were in the colony. The other half were individually housed in metal mesh cages with screens in between to isolate them from other rats (there are some caveats for this for other studies and I’ll get to those at the end).
But the real question for the behavioral pharmacologists following along? How they tracked the drug use. All the rats initially had no experience with morphine. The morphine in this case was delivered via sipper tubes in what is called a two-bottle choice procedure. The rat gets two sipper tubes to choose from, one with water and one with morphine in the water (the morphine is mixed with sugar because it’s bitter tasting, I’ll have to talk about that at the end too). In an individually housed situation, it’s really easy to use those sipper tubes to track how much the rat drinks and of what. But in a colony?! You’d have all the rats sipping from the other rat’s drinking tubes and giving each other cooties and who knows whatall.
But these guys had a clever system. They put the sipper tubes at the end of a skinny tunnel which could only admit one rat at a time. The sippers were controlled by a nose-poke device, where they would only let out a specific amount of liquid at a time and only when a rat nose-poked correctly. And then the authors LABELED all the rats (the rats were albino and got their fur dyed) so they could videotape to see who was who, when they were drinking, and correlate that with the amount dispensed at the time to come up with exactly how much an individual rat drank. Remember, this was back in the 70’s, now we could probably do it with identifying microchips which would record each rat’s intake at the sipper tube, but back then they didn’t have that.
So, we have rats in a colony, and rats singly housed. We have morphine. What’d they get.
Looks pretty clear, don’t it. The individually housed rats drank a LOT more morphine solution than did colony housed rats. The total amounts of liquid consumed (morphine and water together) were not different, which suggests that the individually housed rats preferred the morphine drink over the water alone. Female rats uniformly drank more morphine than males, which is SUPER interesting, but which the authors don’t really discuss. I find that happens a lot in these sorts of papers, the females do something different, and…the authors don’t know what to make of it and let it alone. I detect a need for a sex-based study.
Simple paper, small findings, but this paper is mentioned in almost every behavioral pharmacology course Sci has ever heard of. The authors of the paper thought at the time that perhaps the socially isolated rats were drinking more morphine to relieve their anxiety at being alone. Perhaps the colony rats were drinking less morphine because it interfered too much with their normal rat behaviors.
There’s one option that they don’t mention, but which has since been shown in other papers: individually housed rats have higher levels of STRESS. Individual housing can also produce depressant effects, both of which could lead to increased morphine intake here.
Now you might think: ok, colony housed rats do less drugs, that’s nice. It’s actually very important for several reasons. First, it implies that individual housing is not best for the rats. This is a known quantity. In fact, the rats in this study were much more stringently housed than rats in most studies, who can see and hear (and sometimes sniff well at) other rats nearby. Not only that, in most studies rats are pair housed with a buddy until they are needed, which alleviates the problems somewhat.
But the other important thing about this study was that it was one of the first studies to really show that social contact, or lack thereof, translated to changes in drug self-administration. Studies like these are quite clearly applicable to the human condition, and some studies (especially those in monkeys) have investigated this further, looking at drug intake not just in social housing, but in RANK among socially housed animals. After all, if we look for the rats that would STILL drink morphine despite being in an optimal situation, we may have found a closer model of drug abuse and addiction in humans
But of course, while colony housing may better mimic a human condition (or a normal rat condition), there are issues. The first is the drug itself. While drugs like morphine and ethanol can be tested in conditions like these with sipper tubes, other drugs that need to be studied, like cocaine or amphetamine, cannot. Drugs like cocaine get a lot of their “high” effects from speed of onset, and drinking from a sipper tube just isn’t going to cut it. Most studies looking at cocaine self-administration have to use i.v. administration through catheters to a vein in the rat. This is quite stable and works really well…until you introduce other rats. A rat can’t reach his back, and so usually can’t reach the catheter, but another rat…can chew your experiment to pieces. So a lot of studies looking at various drugs need to usual individually housed rats for viable data.
There’s also the issue in this paper of the isolation that the isolated rats underwent. It was a bit extreme, blocking the sight of other rats and all. Normal individual housing of rats is not like that, and so the effects might be less.
Finally, there’s the sweet spot issue here: SUGAR. Morphine is very bitter, and to make it palatable, it needs to be mixed with sugar. Unfortunately, this does two things: (1) makes the morphine solution have caloric value and (2) makes the morphine solution sweet and tasty. So what they needed to include here was a control of JUST sweetened water. As it was, the rats drank the most when there was the least morphine and the most sucrose present, which makes ME wonder if they were really just after the sugar. This wouldn’t necessarily be a bad thing, sugar is a reinforcer and would be a good thing to look at in socially vs individually housed rats, but I think I want proof that the rats are drinking for the morphine itself in this particular study, and not the potential sweetness.
Despite all these, it’s an interesting study, and certainly it was one of the first to really show this effect in behavioral pharmacology. And the moral of the story? For happy rats, think rat playgrounds and rat buddies.
Hadaway, P., Alexander, B., Coambs, R., & Beyerstein, B. (1979). The effect of housing and gender on preference for morphine-sucrose solutions in rats Psychopharmacology, 66 (1), 87-91 DOI: 10.1007/BF00431995
