How Animal Research Has Advanced the Understanding of Depression

Animal models have made numerous progresses in the last century. This type of research has made a difference in the way we look at psychological issues such as depression. This paper is a review of the literature on animal models of depression. The issue of what advances have been made will be explored. The effects of serotonin on many issues have been studied. In this paper stress, learning, memory, brain derived neurotrophic factor, ovarian hormone withdrawal, and effects of certain drugs will be looked at. Let's look at stress and serotonin first.

Stress

A study done by Grippo, Sullivan, Damjanoska and colleages (2004) shows that chronic mild stress provokes behavioral and physiological changes and may change serotonin receptor function in rats. In this study sixty four Sprague-Dawley rats were used. Half were male and the other half were female. The following stimuli were used as stressors which include:

Continuous light for 2 12 hour periods

Forty degree tilt along vertical axis of cage for 6 hour period

Paired housing for a 16 hour period and 4 hour period

Damp bedding with 300 mL water spilled on bedding for 16 hour period

Water deprivation for 16 hour period

Empty water bottle following 16 hour water deprivation for 1 hour

Stroboscopic light with 300 flashes a minute for a 6 hour period and 4 hour period

White noise at approximately 90 dB for 4 hour period of continuous noise and a 3 hour period with random intermittent noise

All the stressors were given over a period of one week, and randomly presented for 3 additional weeks for a total of 4 week trial. All the rats were injected with a receptor agonist and were decapitated 15 minutes after the injection for the trunk blood. The 4 week trial resulted in the rats showing signs of depression, and satisfied adrenocorticotropic hormone (ACTH) responses to the receptor agonist. The trials also sparked a lack of pleasure in both male and female rats.

Another studied related to stress was done by Gregus, Wintink, David and Lalynchik (2005). This study looked at corticosterone injections and stress and how this relates to depression. Sixty naпve Long-Evans male rats were used. The rats were randomly assigned to 4 groups and were given corticosterone injections (CORT), vehicle injections, repeated restraint stress and repeated handling. These treatments were given for 21 days. The CORT group and vehicle group were given injections at random times during the light and dark cycles. The restraint stress were given for 6 hours each day at random times during the light and dark cycles. They were placed in a Plexiglass restraint tube. The tubes were small enough to limit the head and limb movements of the rats. In order to control for the handling of the rats the rats in the handling groups were quickly picked up and put back into the home cage. The behavioral testing consisted of an open field and resistance to capture tests. These were done in the light cycle of the light/dark cycles. The injections and restraint manipulations still occurred during the behavior testing. The open field test was done in a black wooden box with no top and a clear Plexiglass bottom with the floor divided into 36 identical squares with tape. This test is frequently used in anxiety testing. After the open field testing the rats were tested in their resistance to capture. An unfamiliar experimenter wore a leather glove and tried to pick the rat up from the top and the resistance was measured on a seven point scale. 0 being the easiest to pick up, 1 vocalizes or shies away from glove, 2, shies sway from hand and vocalizes, 3 runs away from hand, 4 runs away and vocalizes, 5 bites or attempts to bite, 6 begins a jump attack. A forced swim test was also measured for the behavioral testing. The first day of swim testing the rats were place in the swim tank for 15 minutes, and 10 minutes on the second day which was the measured trial for depressive symptoms. The last behavioral testing was a social interaction test. This test was conducted in an unfamiliar white wooden box with not top. The room was brightly lit and box was placed on the floor. Rat from the same experimental groups were place in opposing corners of the box. The behaviors recorded were the amount of time the rats spent in non aggressive interaction, amount of time the rats spent in aggressive interaction and amount of time spent with no reaction at all. A decrease in the interaction was noted as an increase in anxiety. The rats in the CORT groups and restraint groups had effects on body weight gain. The rats with vehicle injections gained more than the CORT injection group. The restraint rats gained less than the handled rats. It was also found that the rats with the CORT injections showed more depressive behaviors than the restraint rats.

Memory and Learning

Animal models have greatly contributed to the knowledge base of depression. Animal models are ideal in studying depression because of the limitations on human research. The next set of studies looked at in this section will look at depression and it's impact on memory and learning.

A study by Sun and Alkon (2004) looked at how induced depression influences learning and memory in 144 male Wistar rats. The two antidepressants used were impramine and buspirone. The vehicle control used was these drugs solubilized in saline. The rats were put in an open space swim test and observed through a video monitor so the observer would not be seen. The rats were free to swim or not for 15 minutes and then placed back into their home cage. Overall, the rats that were given the vehicle drug showed a decrease in the distance moved over the trials in the swim tests. To see how the induced depression affected the memory and learning in the rats the antidepressants were not given in the memory and learning tasks. The first task was the spatial water maze learning and memory task. The water maze was divided into four quadrants. The control rats were allowed to swim around for 2 minutes without a hidden platform while the treatment rats were on their third day of induced depression. The next day all the rats were given this task and the platform was hidden and the rats were to find it. The rats were allowed to swim around until they found the platform and were left there for 20 seconds. The rats that did not find the platform in 2 minutes were guided there. After the training trials the platform was removed and the rats were tested for memory of the

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