Research Paper on Lithium Chloride's Impact on Exploratory Behaviour & Innate Fear

Introduction

Previous studies (such as Tenk et al.) have provided evidence that application of Lithium Chloride (LiCl) in animals reduces their horizontal and vertical activities, which is interpreted as lessened exploratory behavior (Tenk, et al. 1072). In another study that was conducted by Tenk et al. in 2005 showed that LiCl reduces, or suppresses locomotor activity and ambulation in rats that are placed in an open field environment (Tenk, et al. 120). In addition to that, an earlier study by Weischer in 1979 found out that LiCl diminished the curiosity of isolated mice (Weischer 266). Also, in a study that was conducted by Johnson in 1976 provided evidence to show that the administration of LiCl altered rat's behavior (Johnson 212).

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Lithium Chloride was first pharmacologically used for the treatment of gout in 1817 (Shorter 5). In the 1940s, it was used on psychiatric patients because of its prophylactic effect on recurrent depression (Licht 219). After the anti-maniac effects of Lithium Chloride were discovered, it has been used for the treatment of the bipolar disorder (BD) in acute and maintenance of depression and mania for over sixty years (Cappeliez and Moore 350). LiCl is considered effective in the treatment of Manic episodes of Bipolar disorder, and therefore, it can reduce risk-taking behavior in the affected patients. The LiCl is thought to affect or alter behavioral tendencies (Van Enkhuizen et al. 3460). The researcher in this study will be interested in measuring or assessing the behavioral changes that result after the administration of LiCl.

The purpose of this study is to examine the effects of 1% LiCl on both the exploratory behavior and innate feat of rats. One subset of rats (n=4) will be injected with 1%LiCl, and the other (n=4) will be injected with saline (NaCl). One-hour post-injection, each of the rats will be placed in a 4*4-foot empty box and observed for 10 minutes. There are several measures that will be recorded to quantify the behavioral changes in the two subsets of rats-number of times the rats enter the center of the field, amount of time a rat spends in the center of the field and number of tile crossings (measures locomotor behavior). The study results that will be generated in this study have the potential to show the effects of LiCl on the behavior and risk-averse tendencies of the rats. Based on the findings of previous studies (some of which have been mentioned in this introduction section), that the LiCl-injected rats will have fewer total line crossings, center entries and less time spent in the center of the open field than is the case in the control group. If this is the case, it will be an indicator of the diminishing or attenuating effect of LiCl on exploratory behavior, and potentiating effect on innate fear.

Material and Methods

The study subjects were eight rats weighing approximately 424.1667 grams (g). The rats were administered with a 1% LiCl solution at 85mgs/kg, or an equivalent volume of saline (depending on their classified subset) intraperitoneally one hour before performing the open field test. This amounted to 3.604 ml of a 1% solution for rats that weighed 424g. All the rats that were used for this experiment or study were exposed to the same conditions except for the solutions that were administered to the rats that were categorized in the two sub-sets of this study.

The apparatus that was used in this study was a 4*4-foot open enclosed box apparatus. The test was conducted with the ceiling lights above the apparatus switched off as too much light increases fear in the subjects. Also, the test was conducted in a quiet place. The observations of the three measures were carried out by three human researchers. There was one researcher who measured the number of times the rats ventured into the center of the apparatus, another measured the total amount of time a rat spent in the center of the apparatus, and the third measured the number of times a rat crossed a floor tile line.

Each rat was placed in the apparatus for 10 minutes. The behavioral data that was observed was recorded and analyzed using Excel. A two-sample t-test was performed with the assumption that there were equal variances, and P-values were calculated. Significance was designated as p<0.05.

Results

The effects of LiCl on exploratory behavior in these rats is shown in figure 1, detailed by the total line crossings variable. In this study, the rats that were administered with Lithium Chloride has fewer total line crossings than the rats that were administered with saline (mean was 42.25 (LiCl) and 53.25 (Saline), p-value= 0.055243775, t-Stat=2.373663, df=6; Fig.1). However, the findings of this study did not show a significantly decreased number of time the experimental rats entered the center of the apparatus in comparison to the controlled rats (mean values = 3.5 (LiCl) and 3.25 (NaCl), p-value= 0.017457189, t-Stat= 3.250418033, df=6; Fig.2). Innate fear was measured using the total amount of time rats spent in the center of the apparatus. The results of this observation were found to be insignificant (13.1625 (LiCl) and 8.5025 (NaCl), p=0.060245343, t-Stat=2.310284508, df=6; Figure 3).

Figure 1: Mean number of total line crossings by the LiCl injected rats and control subject rats.

Figure 2: Mean number of times the LiCl injected rats entered the center of the apparatus versus the control subject rats.

Figure 3: Mean amount of time (in seconds) spent in the center of the apparatus by the LiCl-Injected rats and the control subject rats

Discussion

The results of this study indicated that LiCl has a measurable impact on the exploratory behavior of rats, as was seen by the significant decrease of line crossings by the Li-Cl injected rats. These results are in agreement with previous similar studies, such as the one that was conducted by Tenk et al. in 2005, whereby the researchers had similar findings. In this study, the researchers observed that the rats that had been injected with the LiCl solution crossed fewer lines within the apparatus than the ones that had been injected with saline. It is an indicator that LiCl has an attenuating effect on exploratory behavior (Tenk, et al. 120).

The results of the study indicated that the amount of times rats entered in the center of the apparatus and amount of time they stayed at the center was insignificant. The researchers interpreted from the observed results that there was no apparent difference in innate fear between the LiCl-injected rats and NaCl-injected rats. The results of this study, contradict earlier findings of Johnson (1976) and Weischer (1979) who conducted similar experiments as is the case in this study. Possible explanations for these disparities may have been prior anxiety of the two subset of rats before the start of the experiment due to them being handled by humans. The disparity of the results could also have been as a result of the observers standing over the apparatus for the whole period of study recording the measures. Their presence and movement could have impacted the results of this study for the two subsets.

To avoid the errors that may have been conducted in this study, in future studies, the rats that will be observed (both for the LiCl and NaCl administered solutions) should be habituated for longer periods. This is meant to increase their familiarity levels with human beings and therefore reduce or eliminate anxiety before the start of the experiment. Also, instead of standing over the apparatus to record the observations, the measures can be recorded using video cameras. This does not only reduce the anxiety of the test subjects but also improves the accuracy of the measurements as the researchers can re-watch the recorded videos to confirm their measures. In future, additional experiments can be conducted to assess the behavioral effects of different dosages of LiCl on rats. It will show the quantity extents of LiCl on behavioral effects on rats, help researchers determine both the upper and lower limits in terms of the response of the drug.

Works Cited

Cappeliez, Philippe, and Elizabeth Moore. "Effects of lithium on an amphetamine animal model of bipolar disorder." Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 14, no. 3, 1990, pp. 347-358.

Johnson, F. N. "Lithium effects upon components of activity in rats." Experientia, vol. 32, no. 2, 1976, pp. 212-214.

Licht, Rasmus W. "Lithium: Still a Major Option in the Management of Bipolar Disorder." CNS Neuroscience & Therapeutics, vol. 18, no. 3, 2011, pp. 219-226.

Shorter, Edward. "The history of lithium therapy." Bipolar Disorders, vol. 11, 2009, pp. 4-9.

Tenk, Christine M., et al. "Dose response effects of lithium chloride on conditioned place aversions and locomotor activity in rats." European Journal of Pharmacology, vol. 515, no. 1-3, 2005, pp. 117-127.

"The effects of acute corticosterone on lithium chloride-induced conditioned place aversion and locomotor activity in rats." Life Sciences, vol. 79, no. 11, 2006, pp. 1069-1080.

Van Enkhuizen, Jordy, et al. "Modeling bipolar disorder in mice by increasing acetylcholine or dopamine: chronic lithium treats most, but not all features." Psychopharmacology, vol. 232, no. 18, 2015, pp. 3455-3467.

Weischer, Marie-Luis. "Influence of Lithium and !ubidium on Exploratory Behaviour and Locomotor activity in Isolated male mice'." Psychopharmacology, vol. 61, 1979, pp. 263-66.

Young, Allan H., and Judith M. Hammond. "Lithium in mood disorders: increasing evidence base, declining use?" British Journal of Psychiatry, vol. 191, no. 6, 2007, pp. 474-476.