In this experiment, I investigated how lithium chloride influences locomotor and exploratory behavior in rat models using a standardized open field paradigm. Lithium is known to modulate intracellular signaling cascades particularly the phosphoinositide and glycogen synthase kinase-3 (GSK-3) pathways, affecting neuronal excitability and synaptic plasticity. After administering lithium or a saline control via intraperitoneal injection, I placed each animal in an open field arena and quantified movement through line crossings and time spent in central versus peripheral zones to assess both motor activity and anxiety related behavior.
Lithium treated rats exhibited a marked reduction in locomotion and exploratory drive compared to controls, consistent with its inhibitory effects on excitatory neurotransmission and motor output. This behavioral outcome provided a clear demonstration of how pharmacological interventions can alter neural signaling at the cellular level and manifest as measurable changes in behavior.
Through this project, I refined my skills in experimental design, behavioral quantification, and statistical analysis, and developed a deeper understanding of the relationship between intracellular signaling, synaptic regulation, and behavioral expression. This experience reinforced my interest in bridging molecular neuroscience with systems level behavior to better understand the neurobiological basis of psychiatric treatments.
Abstract
Lithium chloride is a drug used to mediate the manic stages of people with bipolar disorder. It is believed to decrease symptoms experienced during mania such as impulsiveness, recklessness, and hyperexcitability. Many neurological effects of lithium chloride are still unknown, one being whether lithium chloride decreases risky behavior or movement in general. In this experiment, lithium chloride was used to test the effectiveness in inhibiting exploratory behavior in rats, compared to a controlled saline group. An open field experiment was conducted, and center-crossings and line crossings were documented for each subject group. Results showed that there was no significant decrease with center crossings and time in center with lithium chloride injected rats. However, lithium chloride injected rats also had significantly less line crossings, meaning they had less overall locomotion. Overall, lithium chloride did not show significant effect on exploratory behavior but showed a decrease in general locomotion. Further studies can be conducted and maybe lithium can be a useful medication for the purpose of decreasing mobility in other diseases.
Introduction
Bipolar disorder (BD) is characterized as a rare personality disorder that affects around 2% of the population (Volkmann, 2020) . Recent studies have shown that abnormal white matter tract connectivity between the orbitofrontal cortex and the temporal lobe may play a role since they are related to higher cognitive functions and emotions. Lithium is known to inhibit glycogen synthase kinase 3β, which has effect on both GABA and glutamate receptors. This mechanism helps decrease the range of mood swings for BD patients.
This experiment was done to test the effectiveness of lithium specifically on risk-taking behavior compared to general locomotion. A test group of rats were injected with lithium and individually released into an open field where their line crossings and center crossings were recorded, along with the time spent in the center. This method would show overall locomotion and exploratory behavior which examples risk taking. Conclusive of previous research of the neuropharmacology of lithium, we expected lithium injected rats to show decreased exploratory behavior with less center crossings and center time than the control group.
Materials and Methods
Materials
Test subjects consisted of 16 ten week – old Sprague Dawley male rats from Envigo. Their weights ranged from 269g to 323g. 8 of the rats were injected with a 2% LiCl solution at a dosage of 85mg/kg. The other 8 rats were injected with equal volume 0.9% sodium chloride. Injections were administered intraperitoneally, 1 hour prior to the open field experiment. The rats were given free food and water. All procedures were consistent with the Institutional Animal Care and Use Committee (ACUC) protocol.
Methods
After an hour post injection, each rat was given 8 minutes in the open field. The open field area was a 4 ft by 4 ft area of 16 equally sized squares, where the center 4 squares were defined as the center. During the 8 minutes, lines crossed, time in the center, and center crossings were recorded, as well as a full video recording. The open field was sanitized with 70% ethanol between each test subject.
Statistical Analysis
The mean of the results of the 16 test subjects were used to calculate the plus or minus standard error (SE) and a Two-Sample T test analyses was used. The the referenced significant p value was p<0.05.
Results
Results were gathered after each rat completed 8 minutes in the open field experiment. Rats that received lithium chloride had less mean center crossings compared to rats injected with normal saline (1.6 +/- 0.9 vs. 1.8 +/- 0.39809, p=0.804, Fig. 1a). There was no significant data. The mean time in the center was also insignificant, where lithium injected rats had a less mean time than normal saline injected rats (3.4 +/- 1.9 seconds vs. 5.4 +/- 1.3 seconds p=0.399, Fig. 1b). There was a big significance in the mean total lines crossed. Lithium injected rats had a significantly less mean total line crossing than saline injected rats (74 +/- 16.7 vs. 123.5 +/- 6.7 p=0.015, Fig.1c).
Discussion
In this open field study, we compared the effects of lithium on exploratory behavior and general locomotion. Before this experiment, we hypothesized that lithium would show a decrease in center crossings, a symbol of exploratory behavior. Although there were individual cases where we did witness an inhibition in center crossings, there was no statistical significance in the average data among the 8 rats injected with lithium compared to the control group (fig. 2). Furthermore, there was no significant difference in the time spent in the center between the two groups either. There was, however, a statistically significant difference in total line crossings, where lithium injected rats were showed close to 30% less total line crosses than the normal saline injected rats (fig. 1c). These results show that lithium does not inhibit exploratory and risk taking behavior, rather decreases general locomotion. Lithium can be explored as an option for other hyperkinetic diseases since it has a direct effect on locomotion, but does not seem to be an effective treatment for BD.
c. Mean Line Crossings. NS=No Significance, *=Significance
Fig. 2 complete statistical data of center entries, center time, and total line crossings for each rat.
References
Sato K. Why is lithium effective in alleviating bipolar disorder? Med Hypotheses. 147:110484.
Volkmann C, Bschor T, Köhler S. Lithium Treatment Over the Lifespan in Bipolar Disorders. Front Psychiatry. 11:377
Goes FS. Diagnosis and management of bipolar disorders. BMJ. 381:073591
McCrea SM. Bipolar disorder and neurophysiologic mechanisms. Neuropsychiatry Dis Treat.6:1129-53.