Sad lonely lady rats may really eat their feelings

Jan 04 2012 Published by under Behavioral Neuro

Today we have a study on sad lonely lady rats. And why? Because it's about time we paid attention to the ladies. The vast majority of studies on anything other than reproduction get done in males. Males are thought to be "easier" (you don't have to track the menstrual cycle), and besides, what we find in males should translate to females right? If it's not reproduction, it should be the same, right?

Very wrong. We are finding out more and more that studies in males do NOT translate to females, and that this can have some very drastic consequences for human health.

So let's talk about models of psychiatric disorders in rats. Girl rats. Because it's about time females got some studies of their own. And we're going to do it using lots of pictures. Because a picture is worth 1,000 words. And rats are awfully cute.

Jahng et al. "Hyperphagia and depression-like behavior by adolescence social isolation in female rats" international Journal of Developmental Neuroscience, 2011.

Rats like to live in groups. Social, you know.

And scientists think that social isolation during adolescence can cause depressive symptoms in rats. This would be a useful model for us. Humans with psychiatric problems like depression, bulimia, and anxiety report a lot more social isolation during adolescence than healthy peers. But while these psychiatric problems are actually much more common in girls, almost all studies on rodent social isolation in adolescence have been done in boy rats. And in boy rats, social isolation doesn't work very well. The results on behavioral tests are variable. But what about in girls?

So these authors took some female rats. They waited until rodent "adolescence" (about 28 days after birth).

Then they house some rats together.

Some rats alone.

They just had the rats live this way until they were young adults (about 50 days after birth for rats). During this time, they monitored weight.

Rats that were housed alone weight significantly more than those who were housed in groups (obviously they all gained weight because they were all growing, but rats housed alone grew a lot more). It wasn't a matter of single rats having more food, all rats got as much to eat as they wanted. But lonely rats weighed more, and started packing on the weight almost immediately after being housed alone.

You can see that food intake increased pretty drastically even in the first week after the rats were housed alone. Were they lonely? Possibly, you can't really ask a rat. Were they bored? Also possible (to control for this they would have to control for enrichment of the rats with toys or running wheels). But for whatever reason, the socially isolated lady rats weighed more.

To get at other aspects of the behavior, the rats got plied with cookies in addition to their normal food.

The single housed rats ate MORE cookies when tested than the group housed rats. Not only did they eat more in general, they also ate more of a high calorie, highly rewarding food. Unfortunately, the authors didn't really look at other differences in reward related systems. Instead, they looked at anxiety.

The single housed rats ran around more in an open field than their group housed lady friends. This could mean that the single housed lonely rats had differences in anxiety related behavior, so the authors put them in an elevated plus maze.

This is a rat in a plus maze. The maze is off the ground, with two arms that have walls, and two that do not. The rats generally prefer the arms with walls, preferring small spaces. An anxious rat will spend more time in the walled arms, while a relaxed rat will explore the open arms more.

But you can see there's not much difference. This could be due to a few things. The lonely rats could really not be more anxious, or it could be that they simply don't show a difference in that test. The authors would have to do other tests, like an open field test (seeing how much a rat likes the open area of a big box, which they generally don't) or a novelty test (how quickly a rat approaches a novel food item) to really be sure.

Because it does appear that these rats have some stress-related differences that could make them more anxious.

This is a measure of corticosterone, a stress hormone in rats (which corresponds to cortisol in humans). The single housed ladies had higher baseline levels of corticosterone than their group housed friends, though they responded to stress in a similar way (though what that means for the hypothalamic pituitary axis SYSTEM, they didn't test. They would have to look at receptor levels to get an idea). Still, it appears that, at baseline, these singly housed rats may be more stressed.

Finally, what does this mean for depression? You can't ask the rat directly, but you can look at behaviors related to things like despair, as in the forced swim test.

This is a rat in a forced swim test. It's in a beaker of water so it can't touch the bottom. Rats are good swimmers and it will swim for a while, climbing the walls and trying to find a way out. How soon it gives up is thought to be a measure of depressive-like behavior in rats, with depressed rats giving up soon.

You can see that the single housed ladies showed higher immobility (less swimming) than their grouped friends. They gave up more, and this could mean they have higher antidepressant behavior.

So what does this mean? This study is very preliminary, but it suggests that housing female rats alone as adolescents really changes their depressive-like behaviors, not to mention their food intake and weight, which could have other consequences. The authors could take this study further in a lot of ways. They could look at reward related behavior with more cookies, approach to tasty foods, sucrose drinking, and maybe responses to drugs, not to mention changes in reward related areas of the brain. They could look at anxiety related behaviors, do these animals show different behavioral responses to stress? How are their stress systems altered? They could look at depressive like states, how do these lonely ladies react to antidepressants, is their neurogenesis different?

But it does mean one very important thing. Previous studies have looked at boy rats. And they found no major differences in WEIGHT. These studies looked in girl rats, and found major differences in depressive like behavior (which has been seen in male rats as well), but also found big differences in weight and food intake. And weight and food intake could have many other effects. It's not just enough to look in males anymore. With depressive disorders and anxiety disorders higher in women, it's about time we looked to the lady rats.

Jahng, J., Yoo, S., Ryu, V., & Lee, J. (2012). Hyperphagia and depression-like behavior by adolescence social isolation in female rats International Journal of Developmental Neuroscience, 30 (1), 47-53 DOI: 10.1016/j.ijdevneu.2011.10.001

20 responses so far

  • That's very interesting. I'm curious to know what research has been done/what books exist on researching animal moods and measuring them via proxies?

    Also, I think I have read elsewhere about the difficulties of extrapolating from male studies to female etiology, but how does that compare to the reliability of extrapolating between female animals and female humans?

    Generally, where do I find out more about animal cognition. I have access to a university library. Can swap for physics skillz.

    • scicurious says:

      There's actually a whole literature on "emotional behavior" in animals, mostly as a correlate to humans. Some good ones I have found:
      "The Lonely Mouse" http://www.ncbi.nlm.nih.gov/pubmed/19819265
      Murine models of depression: http://www.ncbi.nlm.nih.gov/pubmed/10591858
      Sex differences in stress responses: http://www.ncbi.nlm.nih.gov/pubmed/21769725

      Obviously this is a lot narrower than "animal cognition" which is a massively wide field.

      And yes, certainly there's an issue extrapolating from female rats to female humans, but it's certainly closer than extrapolating from MALE rats to female humans. We're starting to realize there are strong sex differences in female rats and humans with regard to stress responses, and these can drastically influence how we respond with stress and depressive behaviors.

  • Dr Becca says:

    Great write up, Sci! The eating thing is pretty interesting, because it's opposite from what you see in animals that are stressed as adults, which is that both male and female rats gain less weight than controls. Do you know if the finding is exclusive to social isolation stress, or would other kinds of stress exposure during adolescence have the same effects?

  • JonF says:

    In my experience doing elevated plus maze, the most difficult task is to not have "Open Arms" by Journey running through your head the entire time.

    I have a pair of female rats as pets at home and they both seem to enjoy the company fairly well, and I know one problem with a lot of behavioral stuff is that it's either done exclusively on male animals or males and females are lumped together for stats, which has always driven me up the wall, since you'd never do that with humans and yet researchers do it all the time like crazy. I've measured corticosterone in mice before - not rats - and found big differences between males and females so I'd be wary of looking into that too much, at least. For what it's worth, the females seemed to vary depending on their point in estrus, which I think you can see reflected in the big, ugly error bars on that one.

    As I'm sure you know, the trouble with a lot of behavioral tests is that it's sort of like taking a rodent out of its cage and then asking it to do an SAT test while at Six Flags and thinking that's representative of normal. Great for really obvious things (like, "has profound dementia" versus "doesn't have dementia") but for something relatively subtle like this it can be really tricky to tease it out, even though anyone who has stuck her hand into a single-housed rat cage versus a group-housed one knows there is very much a quantifiable difference. It's just a question of figuring out the most meaningful and reproducible means of quantifying it. The forced swim test might be the best way to go here since it seems there's more of a depression phenotype than an anxiety one in rats, though I'm not sure if that would translate to mice since they're anxious little suckers to begin with.

    • scicurious says:

      Yes, I also think the EPM and other anxiety tests can be difficult in this way. Some scientists prefer things like novelty induced hypophagia as a way to control for this (so you really have only one stressor, all the rest is trained), but it's still an issue.

    • barrylyndon says:

      I know this post is old, but I am wondering whether the forced swim test is an accurate assessment of depression in this study. Is it possible heavier rats might give up sooner as a function of their increased bulk (rather than their experience with isolation?) I imagine they have more difficulty swimming than their lighter counterparts in the first place.

      • Scicurious says:

        Good question. Actually, they did look at things like locomotor activity as a function of weight, etc. There's no difference. In other studies I have seen, heavier rats give up in FST sooner, but this does not appear to be a function of weight (usually as shown by correlation). So I would hypothesize that it's not the weight, but you never know.

  • becca says:

    The alone rat looks very lonely.

    It's interesting they found significance with food intake more easily than weight. I don't know if it's just easier to measure, or if it's possible lonely rats actually moved around more. Or just produced more body heat, they didn't have anyone to cuddle with after all.

    • scicurious says:

      It's possible they were producing more body heat, I don't think that was measured, but IACUC recommendations require that single housed rats and mice get "nestlets" due to the body heat differences, which might control for some of it.

  • Ratgirl13 says:

    Those awful behavioral scientists. As if the wire monkey mothers weren't bad enough, they have to put dear sister ratties in cages all alone and hand them a packages of cookies to see if they scarf down the whole thing just like human females. I fully expect those rodents' gym memberships to be paid in full by the experimenters -- girls want their svelteness back!

    • Ratgirl13 says:

      Actually I have been thinking about why this behavior would be advantageous to rats. I have had a great many pet rats in my life, hence the nickname, and I am thinking that if one lives alone and has no one to forage for food if one cannot, it would make sense to prepare for a disruption in the food supply by consuming extra. There's also no impetus for altruism, for sharing with one's sister so she'll continue to hang around and forage on one's behalf. And no one to fight with over the last cookie...

      Nope, being alone is not a good thing for animals who evolved living in social groups. Twenty-five percent of all American households now have only a single occupant (and many pints of Haagen-Daas).

  • Flow says:

    I think it's interesting to look at the guys conducting this study.
    Looking at their Departments (Department of Oral and Maxillofacial Surgery...yes, has to do with...eating...), what do the local guys think about the research going on under their roof? And who is funding this and not being at least amused about the rough relation? Or was this study just a byproduct? Funny :)!!

  • Amy says:

    Really interesting stuff. Thanks so much for writing this up! It would be interesting to see what kind of differences come from rats housed together for a year or so and then living alone in later life. It would give owners with lonely rats a helping hand to make an informed decision whether to keep them alone or integrate them in a new home with a new mischief of older females (a position I am now in myself). Wish I had the means to do these studies at home.

  • Channy says:

    Ya know, I own 2 lady rats and while I don't really like any rats being tested on, I hear ppl say all the time that rats are useless compared to dogs and so forth. But, if you REALLY think about it, rats have saved WAYYy more human lives than dogs could ever aspire to.
    Thank you to all of the ratties who have saved so many lives by giving theirs. R.I.P.

  • Emily Kleine says:

    Wow that is very interesting because I have a female rat that is all alone ( her sister died of stroke) and she weighs surprisenling more than she did before she was housed alone!:/

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