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
