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November 22, 2008

The HR/LR Model

To start of my blog I’ll give a little background on my own research and the research done at MBNI. My research has focused primarily on the HR/LR model and its uses as a novel rodent model for depression. When I started last September I was introduced to the HR/LR model. The model is based off of loco motor scored in a novel environment, in other words the rat is placed in a new cage and its movement is monitored. In a litter of normal purchased lab rats some show naturally higher loco scores that others. In our original round of breeding we divide these into the high scoring or High Responder (HR) and low scoring or Low Responder (LR) groups. From there HRs are bred with HRs and LRs with LRs etc. As generations pass of these selectively bred animals their loco motor responses become more defined with the LRs consistently more lethargic and the HRs more hyperactive.

Along with these loco characteristics come characteristics involving depression and anxiety. LRs show consistently higher depression scores and anxiety scores while HRs show significantly lower. While it is often hard to determine what makes a rat “depressed” or “anxious” there are several accepted tests that can be markers for these characteristics.

The first is called the Forced Swim Test (FST). In this a bucket is filled with water and the rat is placed in it for 15 minutes. The rat can either float, swim, or climb at the sides, after 15 minutes the rat realizes that it can’t escape, this is a term in psychology referred to as learned helplessness. After the 15 minutes the rats are removed and put back in their cages. 24 hours later the test is run again, but this time only for five minutes. The sign of depression is having significantly more time spent floating or immobile than is spent swimming or climbing. LRs show significantly higher immobility times compared to their HR counterparts.

The second test is called the Open Field Test (OF). In this the rats are placed in a large, typically about three feet by three feet box. Rats are nocturnal animals and generally prefer to stay in dark areas. This is a test of anxiety and it measures the latency of the animal to enter the open center of the box and the total amount of movement. The LRs show increased anxiety and stay primarily in the darkest corners of the box while the HRs enter the center of the box more quickly and are more likely to stay in the center.

The third test is called the Elevated Plus Maze (EPM). In this there is a cross shaped maze that is raised off the ground by about five feet. Two of the arms are enclosed while the other two are open. Much the same as the OF test the EPM tests anxiety by measuring the latency to enter the open arms and the amount of time spent in the open arms. As is to be expected the LRs spend most of their time in the closed arms while HRs are more willing to explore the open arms.

Recently we have decided to test how good a model for depression the HR/LR model really is. We treated HRs and LRs with a common anti-depressant called Paroxatine. With the anti-depressant treatment we found that we were able to significantly decrease the depression characteristics in our LRs. From this we concluded that in fact we had developed a novel model of depression.

Posted by horr at November 22, 2008 11:13 PM