How do you study depression in animals? What do you do, and what does it mean? Scientists have several ways to approach a study of depression in animal models. You can try and knockout specific genes, and see how those genes impact depressive like behaviors. You can try and induce depressive like behaviors by stress or environmental changes. And then you can breed animals together into lines, not for a specific gene, but for a specific behavioral or neurobiological set of responses. In this way scientists have studies alcoholism by breeding alcohol preferring and non-preferring rats, and in this particular study, scientists have studied depression using the flinders sensitive line.
Owens et al. “Sert-ainly slower: Reduced sert expression and function in the flinders sensitive line (fsl) rat model of depression” University of Texas Health Sciences, San Antonio. 343.26, G1.
While we don’t think that low levels of the neurotransmitter serotonin CAUSE depression, scientists do think that serotonin is still involved in major depressive disorder. We know that selective serotonin reuptake inhibitors, which block the serotonin transporter (SERT) and prevent recycling of serotonin, treat depression in patients. And we know that playing around with the serotonin system, changing how serotonin is processed in the brain and the receptors that mediate how the brain responses to serotonin, can change not only whether an animal displays a “depressive like” behavior, but can also determine how they respond to antidepressants.
In the case of the flinders sensitive line, these are rats which were developed in Australia, and were “designed” to have something called a hypercholinergic response. But they ALSO (aside from that) show depressive like behavior. They have decreased social interactions and grooming (big signs of ‘depression’ in rodents), and also show depressive-like responses in tests like the forced swim test, which is often used to model depressive-like activity and responses to antidepressants in rats and mice.
Of course these rats were not BRED originally for these responses, so now scientists have to figure out what is going on. This study looked at the SERT in the flinders sensitive line, how it was working, what might be wrong, and what might be changed in these animals.
They first used a technique called chronoamperometry to look at the function of the SERT. The SERT transports serotonin, after it is released, back into the releasing cells for recycling or breakdown, and so messing with its function can really change how serotonin is being controlled in the brain. The scientists found in this study that the flinders sensitive line has SERT that is…not as “good” as that of normal rats. It doesn’t clear serotonin as well. They thought perhaps it was because of the genetic code for SERT, but that wasn’t it. It turned out that these rats actually make less SERT protein in their brains than normal rats do.
But this wasn’t all. The flinders sensitive rat doesn’t have normal SERT, but when you look at how SERT responds to antidepressants, they saw no differences. Something in the finders sensitive line is compensating, at least partially, for the lower levels of SERT. But what? To authors decided to look at OCT-3, the organic cation transporter-3, which can ALSO take up neurotransmitters in the brain, though it does so with less affinity (meaning, less well) than transporters like SERT. And it looks like the OCT-3 helps make up where the SERT is lacking, and that flinders sensitive rats have higher levels of OCT-3 in areas like the hippocampus, making up for low levels of SERT. They will use future studies to determine if OCT-3 specifically can control antidepressant responses in the flinders sensitive line. And the authors hope that studies in these rats can one day help humans who suffer from depression, and who may have similar changes taking place.