Abstract
Previous findings suggest that Lithium Chloride (LiCl) treats the Manic episodes of Bipolar disorder by alleviating risk-taking behavior. To alter the risk-taking behavior, Lithium chloride (LiCl) is administered and then regulated by Sodium Chloride (NaCl) intake. This experiment was conducted on rats to observe the effect of LiCl consumption on their movements. The rats were given lithium chloride and then later released into the open field apparatus, and then monitored their behaviors by direct observation. Rats administered with LiCl showed a reduction of movements in the open field. This finding suggests that LiCl affects the movement of rats significantly due to its being sedative.
Introduction
Lithium Chloride (LiCl) is used as a modifier of behavior in both humans and rats. It is well-known as effective sedation, controlling erratic behaviors (O’Donnell and Gould 2007). Clinically, lithium chloride (LiCl) has been used to treat manic symptoms presented in people with bipolar disorder (O’Donnell and Gould 2007). In rats, LiCl has been used to modify both exploratory behaviors (Youngs et al., 2006) as well as possible anxiety and innate fear.
The open-field box is typically used to determine changes in overall exploratory behavior and locomotor movements (Seibenhener & Wooten, 2015). This apparatus is mainly used for finding the change in behaviors by measuring the movements. The more fearful a rat seems to be, the more time it will spend near the wall area as they are less likely exposed. The rats with less fear and more exploratory drive tend to explore and spend more time in the exposed central area of the apparatus (Gordon & Adhikari, 2010).
Research by Scotti et al. (2011) used rodents who were induced with manic behaviors to administer lithium chloride to see how it affected their overall behavior. So, using the same procedure to create an experiment to see the relationship between exploratory behaviors and LiCl consumption might yield connections between both variables in behavior modifications. In this experiment, rats were injected with the LiCl solution and were placed in an open field to measure their changes in locomotor behaviors. There are two components in the open field: the center and near the wall area. Each tile on the floor of the open field is used as an indicator of behavior change and monitors their performance in a set of times. If the rat’s movement decreases significantly, administering lithium chloride reduces exploratory behaviors.
Method
Animals and Drugs
Twelve Sprague-Dawley male rats weighing 300g – 350g. Each rat was given 1% of LiCl solution intraperitoneal (I.P.). Rats were given the solution exactly 1 hour before being placed on the open field.
Open-field procedure
Rats were placed on the open field. Then recorded the number of times each rat crossed the line and the time they spent in the center and near the wall area.
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Statistics
All data were analyzed using a two-tailed student’s t-test. P values less than 0.05 were considered significant. Error bars represent the standard error of the mean.
Results
The exploratory behaviors were recorded for each subject by measuring the duration of time they spent in a specific area and how many times they crossed each tile. The rats that were given the LiCl solution showed a reduction in line crossing. Then the rats that were given the LiCl solution had a reduction in the number of times entering the center of the open field box compared to the rats given the NaCl solution (fig.2). finally, the rats that were given LiCl solution had a reduction in the time they spent in the center of the open field box compared to the rats given NaCl solution (fig.3)
Discussion
In this experiment, I found that the exploratory behaviors of rats injected with lithium chloride are far less in comparison to the rats injected with saline. In figure. 1, we can see that rats with Lithium Chloride exhibit a reduction in line crossing in contrast to the rats injected with NaCl (p = 0.044647928). This shows the relationship between lithium chloride and the number of line crossings is borderline significant. But figure 2 and 3 shows statistically significant results on the relationship between differences in movement under the influence of LiCl in comparison to NaCl. In Figure 2, the number of times the rats enter the center of the open field is lower than the rats with NaCl (p = 0.020691019). And in Figure 3, the time the rats spent in the center is less than the rats with NaCl (p = 0.01638023). This suggests the change in locomotor movements and exploratory behaviors are directly proportional to the consumption of LiCl by rats.
As Youngs et al. (2006) suggest, the rodent’s behaviors in open field experiments depend on their innate exploratory behavior against their nature to avert the open space. Rodents tend to avoid taking risks by nature. But under the influence of LiCl, this behavior of the rats seems to be increased and their movements have decreased. From the data above, I think flooding of lithium chloride in the rats’ bodies, causes a paralyzing effect. According to Leeds et al. (2014), LiCl is used as an inhibitor from forming erratic impulses due to its nature of competing with Sodium (Na+), which in turn slows down neural signals. Therefore lithium chloride is mainly used as a sedation to control manic episodes in bipolar patients. As you know, the change in environmental stimulus causes anxiety to trigger behaviors to change from typical ones to defensive ones (Steimer, 2011). So based on our results, we can assume that there is causality between the LiCl consumption and the exploratory behaviors of rats.
Even though the data suggests the cause and effect of these variables are significant, there are many other factors to consider that might influence overall data. This experiment was created using controlled subjects and the environment. However we cannot conclude the results as accurate, as there are more underlying aspects that might skew it. Rats are in vivo subjects which makes it harder to predict their actions. The most common issue is we do not know the overall health conditions or the age groups of the rats We only assumed that all the rats were in perfect health for the sake of the research. Age and health conditions are key components that affect exploratory behaviors. Aging slower the movements because neuronal cells become insensitive to signals. So, when rats avoided moving around, it might simply be age-related. The underlying health condition might also affect the exploratory behaviors as they will avoid putting them at risk when they are weak. Interestingly, rats might simply be tired from the activities they did, before the research begins.
To provide accuracy in our future research, we should use genetically similar and genetically modified rats without any underlying health conditions as test subjects. All the rats should be within a similar age group and should be raised in one environment. This will help to control nature and nurture from distorting the experimental results. We use the same procedures as conducted in this experiment to see whether the results from these two types of research validate each other.
References
- Gordon, J., & Adhikari. (2010). Learned fear and innate anxiety in rodents and their relevance to human anxiety disorders. In H. Simpson, Y. Neria, R. Lewis-Fernández, & F. Schneier (Eds.), Anxiety Disorders: Theory, Research, and Clinical Perspectives (pp. 180-191). Cambridge: Cambridge University Press.
- Leeds, P. R., Yu, F., Wang, Z., Chiu, C. T., Zhang, Y., Leng, Y., Linares, G. R., & Chuang, D. M. (2014). A new avenue for lithium: intervention in traumatic brain injury. ACS Chemical Neuroscience, 5(6), 422–433. https://doi.org/10.1021/cn500040g
- O'Donnell, K. C., & Gould, T. D. (2007). The behavioral actions of lithium in rodent models lead to the development of novel therapeutics. Neuroscience and NCeviews, 31(6), 932–962. https://doi.org/10.1016/j.neubiorev.2007.04.002
- Scotti, M. A., Lee, G., Stevenson, S. A., Ostromecki, A. M., Wied, T. J., Kula, D. J., Gessay, G. M., & Gammie, S. C. (2011). Behavioral and pharmacological assessment of a potential new mouse model for mania. Physiology & behavior, 103(3-4), 376–383. https://doi.org/10.1016/j.physbeh.2011.03.005
- Seibenhener, M. L., & Wooten, M. C. (2015). Use of the Open Field Maze to measure locomotor and anxiety-like behavior in mice. Journal of Visualized Experiments: JoVE, (96), e52434. https://doi.org/10.3791/52434
- Steimer T. (2011). Animal models of anxiety disorders in rats and mice: some conceptual issues. Dialogues in clinical neuroscience, 13(4), 495–506.
- Youngs, R. M., Chu, M. S., Meloni, E. G., Naydenov, A., Carlezon, W. A., Jr, & Konradi, C. (2006). Lithium administration to preadolescent rats causes long-lasting increases in anxiety-like behavior and has molecular consequences. The Journal of neuroscience: the official journal of the Society for Neuroscience, 26(22), 6031–6039. https://doi.org/10.1523/JNEUROSCI.0580-06.2006
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